determination of albendazole in oral suspension

11
This article was downloaded by: [The University of Manchester Library] On: 19 December 2014, At: 20:03 Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK Analytical Letters Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/lanl20 DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION Marlene M. Fregonezi-Nery a , Marcela M. Baracat a , Érika R. M. Kedor-Hackmann b & Rafael Mota Pinheiro a a Centro de Ciências Agrárias Departamento de Tecnologia de Alimentos e Medicamentos, Campus Universitário , Universidade Estadual de Londrina , Cx. Postal 6001, Londrina, PR, 86051-970, U.S.A. b Universidade de São Paulo , Faculdade de Ciências Farmcêuticas, Cidade Universitária, Av. Lineu Prestes, 580, Bloco 13, São Paulo, SP Published online: 02 Feb 2007. To cite this article: Marlene M. Fregonezi-Nery , Marcela M. Baracat , Érika R. M. Kedor-Hackmann & Rafael Mota Pinheiro (2001) DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION, Analytical Letters, 34:8, 1255-1263, DOI: 10.1081/ AL-100104151 To link to this article: http://dx.doi.org/10.1081/AL-100104151 PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions

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Page 1: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION

This article was downloaded by [The University of Manchester Library]On 19 December 2014 At 2003Publisher Taylor amp FrancisInforma Ltd Registered in England and Wales Registered Number 1072954 Registered office MortimerHouse 37-41 Mortimer Street London W1T 3JH UK

Analytical LettersPublication details including instructions for authors and subscription informationhttpwwwtandfonlinecomloilanl20

DETERMINATION OF ALBENDAZOLE IN ORALSUSPENSIONMarlene M Fregonezi-Nery a Marcela M Baracat a Eacuterika R M Kedor-Hackmann b ampRafael Mota Pinheiro aa Centro de Ciecircncias Agraacuterias Departamento de Tecnologia de Alimentos eMedicamentos Campus Universitaacuterio Universidade Estadual de Londrina Cx Postal6001 Londrina PR 86051-970 USAb Universidade de Satildeo Paulo Faculdade de Ciecircncias Farmcecircuticas Cidade UniversitaacuteriaAv Lineu Prestes 580 Bloco 13 Satildeo Paulo SPPublished online 02 Feb 2007

To cite this article Marlene M Fregonezi-Nery Marcela M Baracat Eacuterika R M Kedor-Hackmann amp Rafael Mota Pinheiro(2001) DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION Analytical Letters 348 1255-1263 DOI 101081AL-100104151

To link to this article httpdxdoiorg101081AL-100104151

PLEASE SCROLL DOWN FOR ARTICLE

Taylor amp Francis makes every effort to ensure the accuracy of all the information (the ldquoContentrdquo) containedin the publications on our platform However Taylor amp Francis our agents and our licensors make norepresentations or warranties whatsoever as to the accuracy completeness or suitability for any purpose ofthe Content Any opinions and views expressed in this publication are the opinions and views of the authorsand are not the views of or endorsed by Taylor amp Francis The accuracy of the Content should not be reliedupon and should be independently verified with primary sources of information Taylor and Francis shallnot be liable for any losses actions claims proceedings demands costs expenses damages and otherliabilities whatsoever or howsoever caused arising directly or indirectly in connection with in relation to orarising out of the use of the Content

This article may be used for research teaching and private study purposes Any substantial or systematicreproduction redistribution reselling loan sub-licensing systematic supply or distribution in anyform to anyone is expressly forbidden Terms amp Conditions of access and use can be found at httpwwwtandfonlinecompageterms-and-conditions

PHARMACEUTICAL ANALYSIS

DETERMINATION OF ALBENDAZOLE

IN ORAL SUSPENSION

Marlene M Fregonezi-Nery1 Marcela M Baracat1

Erika R M Kedor-Hackmann2 and

Rafael Mota Pinheiro3

1Universidade Estadual de Londrina Centro de CienciasAgrarias Departamento de Tecnologia de Alimentos eMedicamentos Campus Universitario Cx Postal 6001

86051-970 Londrina ndash PR ndash Brasil2Universidade de Sao Paulo Faculdade de Ciencias

Farmceuticas Cidade Universitaria Av Lineu Prestes580 Bloco 13 ndash Sao Paulo ndash SP

3Universidade Estadual de Londrina Centro de CienciasAgrarias Departamento de Tecnologia de Alimentos e

Medicamentos Campus UniversitarioCx Postal 6001 86051-970

ABSTRACT

Albendazole is a potent benzimidazole anthelmintic used in thetreatment of human intestinal helmintiasis as well as of hydatidcysts and neurocysticercosis Two analytical methods werestandardized for determination of albendazole in pharmaceuti-cal preparations (oral suspension) one by UV direct spectro-photometry at 230 nm using as solvent 2 sulfuric acid inmethanol and another by HPLC using a Nucleosil C18

1255

Copyright amp 2001 by Marcel Dekker Inc wwwdekkercom

Corresponding author E-mail ismaelcambenetcombr or neryuelbr

ANALYTICAL LETTERS 34(8) 1255ndash1263 (2001)

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(5 m 46 150mm) Phenomenex column and a mobilephase consisting of methanol 005M phosphate buffer(7030 vv) UV detection at 254 nm and ambient temperatureThe methods were applied to simulated and commerciallyavailable samples and the results were statistically comparedshowing that both methods were accurate and sensitive andthere was no significant difference between them

INTRODUCTION

Albendazole or carbamic acid [5-(propylthiol)-1H-benzimidazol-2 yl]-methyl ester is a potent antihelintic widely used for therapy of human gastro-intestinal helmintiasis which has also shown efficacy for the treatment ofhydatid (3679) Recently it has been demonstrated that albendazole ishighly effective for the treatment of neurocysticercosis even in those patientswho had shown poor therapeutic response to praziquantel (236)

Although it has been largely studied from the pharmacological point ofview (1510111518) only a few analytical methods have been described(412131416) Most studies refer to its determination in biologic fluidsThe American pharmacopoeia suggests high performance liquid chromato-graphy as method to analyze the raw material (17) Albendazole is commer-cially available as tablets and suspensions The object of this study wasto standardize methods in order to determine the albendazole content inpharmaceutical suspensions commercially available

EXPERIMENTAL

Chemicals

All reagents and solvents were analytical grade Albendazole was kindlydonated by Sanofi Winthop Farmaceutica and was used as a referencechemical substance without further purification samples A and B (commer-cial suspension) C (simulated suspension) 2 sulfuric acid solution inmethanol formic acid solution 1M in methanol 005 potassium dihydrogen-phosphate solution and methanol chromatographic grade

Apparatus

The apparatus used for HPLC system was a Shimadzu modelLC-10AS chromatography pump equipped with a Shimadzu UV SPD-10

1256 FREGONEZI-NERY ET AL

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ultraviolet detector The detector was set at 254 nm Test samples wereinjected using a model 7725 Rheodyne valve with a 20 mL loop and peakareas were integrated automatically by computer For the UV Spectro-photometer Shimadzu ndash model UV-160A was used

Samples

The samples used were Sample A commercially available suspensions4 (produced by Sanfi Winthrop Pharm Ltda Brasil bach 62806NDcontaining 10mL) Sample B commercially available suspensions 4(produced by Smithkline Beecham Laboratory Ltda Brasil bach TLZ0246containing 10mL) and Sample C simulated Suspensions 4

Ultraviolet Spectrophotometry

A 50ml aliquot of commercially available (A and B) and simulated(C) samples equivalent to 2000mg of albendazole were transferred to a200ml volumetric flask 1000ml of 2 sulfuric acid in methanol wereadded and the solution was homogenized for 10 minutes in ultrasoundSolution A was diluted to volume and filtered 50ml of solution A weretransferred to a 100ml volumetric flask and were diluted to volume with 2sulfuric acid in methanol (solution B) 10 aliquots of 50ml of solution Bwere transferred to 10 50ml volumetric flasks and after completing thevolume with distilled water a solution with 50 mg albendazoleml concen-tration was obtained Absorbances of sample solutions were determined in230 nm using 2 sulfuric acid in methanol as a blank Quantification ofresults was made using the calibration curve

Standard Solution

One 50mL aliquot of stock solution (5000 mgmL of albendazole) wastransferred to a 100mL volumetric flask and the volume was reached with asolution of 2 sulfuric acid in methanol obtaining the 250 mgmL concen-tration solution From this solution other solutions with known concentra-tions of albendazole (25 to 75 mgmL) were prepared in distilled waterReadings of absorbances were done at 230 nm after the apparatus was cali-brated with a solution of 2 sulfuric acid in methanol used as a blankReadings were done in three repetitions

ALBENDAZOLE IN ORAL SUSPENSION 1257

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Determination of Calibration Curve

Quantification of results was done through calibration curves obtainedfrom the concentrations of the standard albendazole (25 35 45 55 6575 mgml) and respective absorbances

High Performance Liquid Chromatography (HPLC)

Chromatographic Conditions

The mobile phase is a mixture of methanol phosphate buffer005M (pH 58) (7030 vv) filtered under vacuum through a Milliporesystem filter 022 mm degaseificated with helium The column (Nucleosil

C 18 (5 m 150 460 nm) Phonomenex was kept at room temperature(20ndash25C) The flow rate was kept constant at 10mlmin The absorbanceat 254 nmwas recorded at a sensitivity of 0032 ausf and injection volume of200 ml

Stock Solutions and Standard Curve Preparation

Stock solution of albendazole (5000 mgmL) was prepared in 2 sul-furic acid in methanol Standard samples were prepared by various dilutionsof stock solutions of albendazole with mobile phase consisting of methanolphosphate buffer 005M (7030 vv) to obtain concentration between 01 mg05 mg 20 mg 50 mg 100 mg 150 mgmL Triplicate 20 mL injections weremade into the loop for each solution and the peak area ratio of albendazolewas plotted against the corresponding concentration to obtain the calibra-tion graph The standard curve was linear (r2gt0999) over the workingrange of the study

Sample Analysis

Five milliliters of commercially available (A and B) and simulated(C) suspensions equivalent to 2000mg of albendazole were quantitativelytransferred to a 200ML volumetric flask containing 500mL of formic acid1M in methanol After total dissolution helped with ultrasound for10 minutes the volume was reached with the same solution The solution wasfiltered through a 022 mm filter A solution containing 50 mgmL of albenda-zole was obtained after two subsequent dilutions of the filtered solution

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The albendazole and the respective concentrations expressed in mgmlwere obtained from the calibration curve Ten determinations for eachsample were done and the results were expressed in mg of albendazolemLof suspension

COMPARISON OF SPECTROPHOTOMETRIC

METHOD IN ULTRAVIOLET AND HIGH

PERFORMANCE LIQUID CHROMATOGRAPHY

Accuracy of the proposed methods was compared through varianceanalysis (ANOVA) using the Snedecor F test and the precision using StudantT test The SAS (Statistical Analyses System ndash 1997) software was used

RESULTS AND DISCUSSION

The results obtained in the standardization through the spectrophoto-metric method in ultraviolet aiming at verifying the method linearity showedthat the albendazole solutions presented linear correlation between absor-bances at 230 nm and the concentrations in the interval 25 to 75 mgmL ofalbendazole with a coefficient of correlation of 09995 (Table 1)

The results from the use of the spectrophotometric method in UV foranalysis of commercially available (A and B) and simulated (C) samples areshown in Table 2 These results showed that the method is accurate withcoefficients of variation of 073 067 and 062 for the average of tendeterminations of samples A B and C respectively

Results of albendazole recuperation in commercially available(A and B) and simulated (C) samples are shown in Table 2 The 9960 to10142 recuperation confirms the method accuracy ie there is a con-cordance between the obtained and the theoretical results

ALBENDAZOLE IN ORAL SUSPENSION 1259

Table 1 Statistical Analysis of the Determination of Albendazole by UVSpectrophotometric and High Performance Liquid Chromatography (HPLC)

Method

MethodLinear Range

(mgmL) Slope Intercept r

UV 2575 102 101 47 103 09995

HPLC 01150 75 105 204 102 09999

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The standardization of the chromatographic method for albendazole

determination showed a linear correlation with a 09999 coefficient of cor-

relation between the peak area and the 01 to 150 mgmL albendazole con-

centration (Table 1)

In Table 2 the low variation coefficients (084 175 078)

obtained by the HPLC method for analysis of commercially available

(A and B) and simulated (C) samples confirm the accuracy of this

method The method precision is also confirmed by the results obtained in

the recuperation test It can be checked in Table 3 that there was a slight

variation in percentage of recuperation 9957 to 10083 in relation to

the quantity added

Detection of interferents from the formulation excipients indicated

that they do not influence either method studied

Comparison of accuracy for both methods was made by the F test

where variance of both methods are compared By the results obtained

(Table 4) it was concluded that there is no significant difference at the 5

level between the proposed methods concerning accuracy

For comparison of precision the T test was used With this test it is

possible to assess if the averages of the experimental values of two proposed

methods UV and HLPC show significant difference at the 5 level Table 5

shows the statistical results obtained estimated from a total of 16 degrees of

freedom whose t value calculated of 11463 was lower than t tabulated of

2201 for 95 Thus the two methods do not show significant difference

concerning precision

1260 FREGONEZI-NERY ET AL

Table 2 Statistical Data Obtained in the Determination of the AlbendazoleContent in Commercially Available (A and B) and Simulated (C) Samples by theUV Spectrophotometric Method and High Performance Liquid Chromatography

Method Sample

DeclaredAmount(mg)

FoundAmount(mg)

Coefficientof Variation

()

ConfidenceLimit

Pfrac14 95

A 40000 38155 073 38155plusmn198

UV B 40000 38624 067 38624plusmn185C 40000 42110 062 42110plusmn180

A 40000 38840 084 3884plusmn232HPLC B 40000 37280 175 37280plusmn468

C 40000 42716 078 42710plusmn256

Average of 10 determinations

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CONCLUSION

The methods proposed for determination of albendazole in oral sus-pension showed linear correlation were accurate exact and did not show

ALBENDAZOLE IN ORAL SUSPENSION 1261

Table 4 Experimental Data obtained from Analysis of Variance (ANOVA) WhenComparing Accuracy of Methods UV and HPLC

Resons forVariation

Degree ofLiberty Square Sum Square Mean F PrgtF

Sample 2 162214 81107 57030 00001Treatment 1 063 063 044 05075

Error 56 7964 14Total 59 170241

Table 3 Results of Albendazole Recuperation of Commercially Available (A andB) and Simulated (C) Samples by the UV Spectrophotometric Method and HighPerformance Liquid Chromatography

Method Sample Added (mg) Found (mg) Recovery ()

250 251 10040A 350 352 10057

450 455 10110

250 250 10000UV B 350 349 9971

450 451 10020

250 252 10080C 350 355 10140

450 448 9960

500 498 9960A 600 605 10083

700 703 10043

500 501 10020HPLC B 600 599 9933

700 697 9957

500 500 10000C 600 603 10050

700 701 10014

Average of 2 determinations

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significant statistical difference concerning accuracy nor exactness

Therefore it is possible to use either of the two methods for the analysis

of albendazole in oral suspensions and the choice will depend on method

cost and benefit

REFERENCES

1 Barragry T Anthelmintics a review N Z Vet J 1984 32 161ndash164

2 CookGCUse of benzimidazole chemotherapy in human helminthiases

indications and efficacy Parasitol Today 1990 6(4) 133ndash136

3 Coulaud JP Rossingnol JF Albendazole a new single dose anthel-

mintic Acta Trop 1984 45 87ndash90

4 Gasparine EA Atualizac ao em parasitoses intestinais J Bras Med

1995 68 (4)

5 Bandres JC Clinton White A Jr Samo T Murphy EC Harris

RL Extraparenchymal neurocysticercosis Report of five cases andreview of management Clin Infect Dis 1992 15 799ndash811

6 Alvinerie M Galtier P Simultaneous determination of albendazole

and its principal metabolites in plasma by normal phase high-

performance liquid chromatography J Pharm Biomed Anal 1984

2 73ndash79

7 Bogan JA Marriner S Analysis of benzimidazoles in body fluids by

high-performance liquid chromatography J Pharm Sci 1980 69

422ndash423

8 Hoaksey PE Awadzi K Ward SA Conventry PA Orne MLE

Edwards G Rapid and sensitive method for the determination of alben-

dazole sulphoxide in biological fluids J Chromatogr 1991 566(1)

244ndash249

1262 FREGONEZI-NERY ET AL

Table 5 Results Obtained When Comparing Accuracy ofProposed Methods Using the t Test

Parameters UV HPLC

x 10042 10012

S 061 047n 10 10

Ttabulated for 16 degrees of liberty (Pfrac14 95)frac14 20101

Tcalculated frac14 11463 xxfrac14Mean of experimental values ()S frac14 Standard deviation nfrac14Number of determinations

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9 Hurtado M Medina MT Sotelo J Jung H Sensitive high

performance liquid chromatographic assay for albendazole and its

main metabolite albendazole sulphoxid in plasma and cerebrospinal

fluid J Chromatogr 1989 494 403ndash407

10 Meulemans A Giovangeli MD Mohler J Vulpillat M Hay

JM Saimot AG High performance liquid chromatography of

albendazol and its sulfoxide metabolite in human organs and fluids

during hydatidosis J Liq Chromatog 1984 7 569ndash580

11 Zeugin T Sysset T Cotting J Therapeutic monitoring of albenda-

zole a high performance liquid chromatography method for determi-

nation of its active metabolite albendazole sulfoxid Ther Drug Monit

1990 12 187ndash190

12 Bergold AM Korolkovas A Doseamento do albendazol como

materia prima e em comprimidos em meio nao aquoso com acido

perclorico Rev Farm Bioquim S Paulo 1993 29(1) 31ndash34

13 Laurentis N Milillo MA Bruno S Determination of albendazole

as raw material and in tablets by nonaqueous tituration with sodium

methylate solution Rev Farm Bioquim S Paulo 1997 33(1) 23ndash27

14 Long AR Hsieh LC Short CR Barker SA Isocratic liquid

chromatographywith photodiode array characterization JChromatogr

1989 475 404ndash411

15 Mandal SC Bhattacharyya M Maity AK Gupta BK Ghosal

SKL Determination of albendazole in tablet formulations by UV

spectrophotometric method Indian Drugs 1992 29(7) 323ndash324

16 Sane RT Samant RS Joshi MD Purandare SM Tembe PB

Nayak VG High performance liquid chromatographic determination

of albendazole in pharmaceuticals Indian Drugs 1989 26 494ndash496

17 United States pharmacopeia 23 ed Rockiville United States

Pharmacopeial Convention 1995 37ndash38 1957ndash1963

18 Dicionario de especialidades farmaceuticas 26 ed Rio de Janeiro

Publicac oes Cientıficas 19971998

Received July 31 2000

Accepted February 13 2001

ALBENDAZOLE IN ORAL SUSPENSION 1263

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Page 2: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION

PHARMACEUTICAL ANALYSIS

DETERMINATION OF ALBENDAZOLE

IN ORAL SUSPENSION

Marlene M Fregonezi-Nery1 Marcela M Baracat1

Erika R M Kedor-Hackmann2 and

Rafael Mota Pinheiro3

1Universidade Estadual de Londrina Centro de CienciasAgrarias Departamento de Tecnologia de Alimentos eMedicamentos Campus Universitario Cx Postal 6001

86051-970 Londrina ndash PR ndash Brasil2Universidade de Sao Paulo Faculdade de Ciencias

Farmceuticas Cidade Universitaria Av Lineu Prestes580 Bloco 13 ndash Sao Paulo ndash SP

3Universidade Estadual de Londrina Centro de CienciasAgrarias Departamento de Tecnologia de Alimentos e

Medicamentos Campus UniversitarioCx Postal 6001 86051-970

ABSTRACT

Albendazole is a potent benzimidazole anthelmintic used in thetreatment of human intestinal helmintiasis as well as of hydatidcysts and neurocysticercosis Two analytical methods werestandardized for determination of albendazole in pharmaceuti-cal preparations (oral suspension) one by UV direct spectro-photometry at 230 nm using as solvent 2 sulfuric acid inmethanol and another by HPLC using a Nucleosil C18

1255

Copyright amp 2001 by Marcel Dekker Inc wwwdekkercom

Corresponding author E-mail ismaelcambenetcombr or neryuelbr

ANALYTICAL LETTERS 34(8) 1255ndash1263 (2001)

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(5 m 46 150mm) Phenomenex column and a mobilephase consisting of methanol 005M phosphate buffer(7030 vv) UV detection at 254 nm and ambient temperatureThe methods were applied to simulated and commerciallyavailable samples and the results were statistically comparedshowing that both methods were accurate and sensitive andthere was no significant difference between them

INTRODUCTION

Albendazole or carbamic acid [5-(propylthiol)-1H-benzimidazol-2 yl]-methyl ester is a potent antihelintic widely used for therapy of human gastro-intestinal helmintiasis which has also shown efficacy for the treatment ofhydatid (3679) Recently it has been demonstrated that albendazole ishighly effective for the treatment of neurocysticercosis even in those patientswho had shown poor therapeutic response to praziquantel (236)

Although it has been largely studied from the pharmacological point ofview (1510111518) only a few analytical methods have been described(412131416) Most studies refer to its determination in biologic fluidsThe American pharmacopoeia suggests high performance liquid chromato-graphy as method to analyze the raw material (17) Albendazole is commer-cially available as tablets and suspensions The object of this study wasto standardize methods in order to determine the albendazole content inpharmaceutical suspensions commercially available

EXPERIMENTAL

Chemicals

All reagents and solvents were analytical grade Albendazole was kindlydonated by Sanofi Winthop Farmaceutica and was used as a referencechemical substance without further purification samples A and B (commer-cial suspension) C (simulated suspension) 2 sulfuric acid solution inmethanol formic acid solution 1M in methanol 005 potassium dihydrogen-phosphate solution and methanol chromatographic grade

Apparatus

The apparatus used for HPLC system was a Shimadzu modelLC-10AS chromatography pump equipped with a Shimadzu UV SPD-10

1256 FREGONEZI-NERY ET AL

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ultraviolet detector The detector was set at 254 nm Test samples wereinjected using a model 7725 Rheodyne valve with a 20 mL loop and peakareas were integrated automatically by computer For the UV Spectro-photometer Shimadzu ndash model UV-160A was used

Samples

The samples used were Sample A commercially available suspensions4 (produced by Sanfi Winthrop Pharm Ltda Brasil bach 62806NDcontaining 10mL) Sample B commercially available suspensions 4(produced by Smithkline Beecham Laboratory Ltda Brasil bach TLZ0246containing 10mL) and Sample C simulated Suspensions 4

Ultraviolet Spectrophotometry

A 50ml aliquot of commercially available (A and B) and simulated(C) samples equivalent to 2000mg of albendazole were transferred to a200ml volumetric flask 1000ml of 2 sulfuric acid in methanol wereadded and the solution was homogenized for 10 minutes in ultrasoundSolution A was diluted to volume and filtered 50ml of solution A weretransferred to a 100ml volumetric flask and were diluted to volume with 2sulfuric acid in methanol (solution B) 10 aliquots of 50ml of solution Bwere transferred to 10 50ml volumetric flasks and after completing thevolume with distilled water a solution with 50 mg albendazoleml concen-tration was obtained Absorbances of sample solutions were determined in230 nm using 2 sulfuric acid in methanol as a blank Quantification ofresults was made using the calibration curve

Standard Solution

One 50mL aliquot of stock solution (5000 mgmL of albendazole) wastransferred to a 100mL volumetric flask and the volume was reached with asolution of 2 sulfuric acid in methanol obtaining the 250 mgmL concen-tration solution From this solution other solutions with known concentra-tions of albendazole (25 to 75 mgmL) were prepared in distilled waterReadings of absorbances were done at 230 nm after the apparatus was cali-brated with a solution of 2 sulfuric acid in methanol used as a blankReadings were done in three repetitions

ALBENDAZOLE IN ORAL SUSPENSION 1257

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Determination of Calibration Curve

Quantification of results was done through calibration curves obtainedfrom the concentrations of the standard albendazole (25 35 45 55 6575 mgml) and respective absorbances

High Performance Liquid Chromatography (HPLC)

Chromatographic Conditions

The mobile phase is a mixture of methanol phosphate buffer005M (pH 58) (7030 vv) filtered under vacuum through a Milliporesystem filter 022 mm degaseificated with helium The column (Nucleosil

C 18 (5 m 150 460 nm) Phonomenex was kept at room temperature(20ndash25C) The flow rate was kept constant at 10mlmin The absorbanceat 254 nmwas recorded at a sensitivity of 0032 ausf and injection volume of200 ml

Stock Solutions and Standard Curve Preparation

Stock solution of albendazole (5000 mgmL) was prepared in 2 sul-furic acid in methanol Standard samples were prepared by various dilutionsof stock solutions of albendazole with mobile phase consisting of methanolphosphate buffer 005M (7030 vv) to obtain concentration between 01 mg05 mg 20 mg 50 mg 100 mg 150 mgmL Triplicate 20 mL injections weremade into the loop for each solution and the peak area ratio of albendazolewas plotted against the corresponding concentration to obtain the calibra-tion graph The standard curve was linear (r2gt0999) over the workingrange of the study

Sample Analysis

Five milliliters of commercially available (A and B) and simulated(C) suspensions equivalent to 2000mg of albendazole were quantitativelytransferred to a 200ML volumetric flask containing 500mL of formic acid1M in methanol After total dissolution helped with ultrasound for10 minutes the volume was reached with the same solution The solution wasfiltered through a 022 mm filter A solution containing 50 mgmL of albenda-zole was obtained after two subsequent dilutions of the filtered solution

1258 FREGONEZI-NERY ET AL

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ORDER REPRINTS

The albendazole and the respective concentrations expressed in mgmlwere obtained from the calibration curve Ten determinations for eachsample were done and the results were expressed in mg of albendazolemLof suspension

COMPARISON OF SPECTROPHOTOMETRIC

METHOD IN ULTRAVIOLET AND HIGH

PERFORMANCE LIQUID CHROMATOGRAPHY

Accuracy of the proposed methods was compared through varianceanalysis (ANOVA) using the Snedecor F test and the precision using StudantT test The SAS (Statistical Analyses System ndash 1997) software was used

RESULTS AND DISCUSSION

The results obtained in the standardization through the spectrophoto-metric method in ultraviolet aiming at verifying the method linearity showedthat the albendazole solutions presented linear correlation between absor-bances at 230 nm and the concentrations in the interval 25 to 75 mgmL ofalbendazole with a coefficient of correlation of 09995 (Table 1)

The results from the use of the spectrophotometric method in UV foranalysis of commercially available (A and B) and simulated (C) samples areshown in Table 2 These results showed that the method is accurate withcoefficients of variation of 073 067 and 062 for the average of tendeterminations of samples A B and C respectively

Results of albendazole recuperation in commercially available(A and B) and simulated (C) samples are shown in Table 2 The 9960 to10142 recuperation confirms the method accuracy ie there is a con-cordance between the obtained and the theoretical results

ALBENDAZOLE IN ORAL SUSPENSION 1259

Table 1 Statistical Analysis of the Determination of Albendazole by UVSpectrophotometric and High Performance Liquid Chromatography (HPLC)

Method

MethodLinear Range

(mgmL) Slope Intercept r

UV 2575 102 101 47 103 09995

HPLC 01150 75 105 204 102 09999

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The standardization of the chromatographic method for albendazole

determination showed a linear correlation with a 09999 coefficient of cor-

relation between the peak area and the 01 to 150 mgmL albendazole con-

centration (Table 1)

In Table 2 the low variation coefficients (084 175 078)

obtained by the HPLC method for analysis of commercially available

(A and B) and simulated (C) samples confirm the accuracy of this

method The method precision is also confirmed by the results obtained in

the recuperation test It can be checked in Table 3 that there was a slight

variation in percentage of recuperation 9957 to 10083 in relation to

the quantity added

Detection of interferents from the formulation excipients indicated

that they do not influence either method studied

Comparison of accuracy for both methods was made by the F test

where variance of both methods are compared By the results obtained

(Table 4) it was concluded that there is no significant difference at the 5

level between the proposed methods concerning accuracy

For comparison of precision the T test was used With this test it is

possible to assess if the averages of the experimental values of two proposed

methods UV and HLPC show significant difference at the 5 level Table 5

shows the statistical results obtained estimated from a total of 16 degrees of

freedom whose t value calculated of 11463 was lower than t tabulated of

2201 for 95 Thus the two methods do not show significant difference

concerning precision

1260 FREGONEZI-NERY ET AL

Table 2 Statistical Data Obtained in the Determination of the AlbendazoleContent in Commercially Available (A and B) and Simulated (C) Samples by theUV Spectrophotometric Method and High Performance Liquid Chromatography

Method Sample

DeclaredAmount(mg)

FoundAmount(mg)

Coefficientof Variation

()

ConfidenceLimit

Pfrac14 95

A 40000 38155 073 38155plusmn198

UV B 40000 38624 067 38624plusmn185C 40000 42110 062 42110plusmn180

A 40000 38840 084 3884plusmn232HPLC B 40000 37280 175 37280plusmn468

C 40000 42716 078 42710plusmn256

Average of 10 determinations

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CONCLUSION

The methods proposed for determination of albendazole in oral sus-pension showed linear correlation were accurate exact and did not show

ALBENDAZOLE IN ORAL SUSPENSION 1261

Table 4 Experimental Data obtained from Analysis of Variance (ANOVA) WhenComparing Accuracy of Methods UV and HPLC

Resons forVariation

Degree ofLiberty Square Sum Square Mean F PrgtF

Sample 2 162214 81107 57030 00001Treatment 1 063 063 044 05075

Error 56 7964 14Total 59 170241

Table 3 Results of Albendazole Recuperation of Commercially Available (A andB) and Simulated (C) Samples by the UV Spectrophotometric Method and HighPerformance Liquid Chromatography

Method Sample Added (mg) Found (mg) Recovery ()

250 251 10040A 350 352 10057

450 455 10110

250 250 10000UV B 350 349 9971

450 451 10020

250 252 10080C 350 355 10140

450 448 9960

500 498 9960A 600 605 10083

700 703 10043

500 501 10020HPLC B 600 599 9933

700 697 9957

500 500 10000C 600 603 10050

700 701 10014

Average of 2 determinations

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ORDER REPRINTS

significant statistical difference concerning accuracy nor exactness

Therefore it is possible to use either of the two methods for the analysis

of albendazole in oral suspensions and the choice will depend on method

cost and benefit

REFERENCES

1 Barragry T Anthelmintics a review N Z Vet J 1984 32 161ndash164

2 CookGCUse of benzimidazole chemotherapy in human helminthiases

indications and efficacy Parasitol Today 1990 6(4) 133ndash136

3 Coulaud JP Rossingnol JF Albendazole a new single dose anthel-

mintic Acta Trop 1984 45 87ndash90

4 Gasparine EA Atualizac ao em parasitoses intestinais J Bras Med

1995 68 (4)

5 Bandres JC Clinton White A Jr Samo T Murphy EC Harris

RL Extraparenchymal neurocysticercosis Report of five cases andreview of management Clin Infect Dis 1992 15 799ndash811

6 Alvinerie M Galtier P Simultaneous determination of albendazole

and its principal metabolites in plasma by normal phase high-

performance liquid chromatography J Pharm Biomed Anal 1984

2 73ndash79

7 Bogan JA Marriner S Analysis of benzimidazoles in body fluids by

high-performance liquid chromatography J Pharm Sci 1980 69

422ndash423

8 Hoaksey PE Awadzi K Ward SA Conventry PA Orne MLE

Edwards G Rapid and sensitive method for the determination of alben-

dazole sulphoxide in biological fluids J Chromatogr 1991 566(1)

244ndash249

1262 FREGONEZI-NERY ET AL

Table 5 Results Obtained When Comparing Accuracy ofProposed Methods Using the t Test

Parameters UV HPLC

x 10042 10012

S 061 047n 10 10

Ttabulated for 16 degrees of liberty (Pfrac14 95)frac14 20101

Tcalculated frac14 11463 xxfrac14Mean of experimental values ()S frac14 Standard deviation nfrac14Number of determinations

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ry]

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003

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embe

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14

ORDER REPRINTS

9 Hurtado M Medina MT Sotelo J Jung H Sensitive high

performance liquid chromatographic assay for albendazole and its

main metabolite albendazole sulphoxid in plasma and cerebrospinal

fluid J Chromatogr 1989 494 403ndash407

10 Meulemans A Giovangeli MD Mohler J Vulpillat M Hay

JM Saimot AG High performance liquid chromatography of

albendazol and its sulfoxide metabolite in human organs and fluids

during hydatidosis J Liq Chromatog 1984 7 569ndash580

11 Zeugin T Sysset T Cotting J Therapeutic monitoring of albenda-

zole a high performance liquid chromatography method for determi-

nation of its active metabolite albendazole sulfoxid Ther Drug Monit

1990 12 187ndash190

12 Bergold AM Korolkovas A Doseamento do albendazol como

materia prima e em comprimidos em meio nao aquoso com acido

perclorico Rev Farm Bioquim S Paulo 1993 29(1) 31ndash34

13 Laurentis N Milillo MA Bruno S Determination of albendazole

as raw material and in tablets by nonaqueous tituration with sodium

methylate solution Rev Farm Bioquim S Paulo 1997 33(1) 23ndash27

14 Long AR Hsieh LC Short CR Barker SA Isocratic liquid

chromatographywith photodiode array characterization JChromatogr

1989 475 404ndash411

15 Mandal SC Bhattacharyya M Maity AK Gupta BK Ghosal

SKL Determination of albendazole in tablet formulations by UV

spectrophotometric method Indian Drugs 1992 29(7) 323ndash324

16 Sane RT Samant RS Joshi MD Purandare SM Tembe PB

Nayak VG High performance liquid chromatographic determination

of albendazole in pharmaceuticals Indian Drugs 1989 26 494ndash496

17 United States pharmacopeia 23 ed Rockiville United States

Pharmacopeial Convention 1995 37ndash38 1957ndash1963

18 Dicionario de especialidades farmaceuticas 26 ed Rio de Janeiro

Publicac oes Cientıficas 19971998

Received July 31 2000

Accepted February 13 2001

ALBENDAZOLE IN ORAL SUSPENSION 1263

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Order now

Reprints of this article can also be ordered at

httpwwwdekkercomservletproductDOI101081AL100104151

Request Permission or Order Reprints Instantly

Interested in copying and sharing this article In most cases US Copyright Law requires that you get permission from the articlersquos rightsholder before using copyrighted content

All information and materials found in this article including but not limited to text trademarks patents logos graphics and images (the Materials) are the copyrighted works and other forms of intellectual property of Marcel Dekker Inc or its licensors All rights not expressly granted are reserved

Get permission to lawfully reproduce and distribute the Materials or order reprints quickly and painlessly Simply click on the Request PermissionReprints Here link below and follow the instructions Visit the US Copyright Office for information on Fair Use limitations of US copyright law Please refer to The Association of American Publishersrsquo (AAP) website for guidelines on Fair Use in the Classroom

The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

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Page 3: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION

ORDER REPRINTS

(5 m 46 150mm) Phenomenex column and a mobilephase consisting of methanol 005M phosphate buffer(7030 vv) UV detection at 254 nm and ambient temperatureThe methods were applied to simulated and commerciallyavailable samples and the results were statistically comparedshowing that both methods were accurate and sensitive andthere was no significant difference between them

INTRODUCTION

Albendazole or carbamic acid [5-(propylthiol)-1H-benzimidazol-2 yl]-methyl ester is a potent antihelintic widely used for therapy of human gastro-intestinal helmintiasis which has also shown efficacy for the treatment ofhydatid (3679) Recently it has been demonstrated that albendazole ishighly effective for the treatment of neurocysticercosis even in those patientswho had shown poor therapeutic response to praziquantel (236)

Although it has been largely studied from the pharmacological point ofview (1510111518) only a few analytical methods have been described(412131416) Most studies refer to its determination in biologic fluidsThe American pharmacopoeia suggests high performance liquid chromato-graphy as method to analyze the raw material (17) Albendazole is commer-cially available as tablets and suspensions The object of this study wasto standardize methods in order to determine the albendazole content inpharmaceutical suspensions commercially available

EXPERIMENTAL

Chemicals

All reagents and solvents were analytical grade Albendazole was kindlydonated by Sanofi Winthop Farmaceutica and was used as a referencechemical substance without further purification samples A and B (commer-cial suspension) C (simulated suspension) 2 sulfuric acid solution inmethanol formic acid solution 1M in methanol 005 potassium dihydrogen-phosphate solution and methanol chromatographic grade

Apparatus

The apparatus used for HPLC system was a Shimadzu modelLC-10AS chromatography pump equipped with a Shimadzu UV SPD-10

1256 FREGONEZI-NERY ET AL

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ORDER REPRINTS

ultraviolet detector The detector was set at 254 nm Test samples wereinjected using a model 7725 Rheodyne valve with a 20 mL loop and peakareas were integrated automatically by computer For the UV Spectro-photometer Shimadzu ndash model UV-160A was used

Samples

The samples used were Sample A commercially available suspensions4 (produced by Sanfi Winthrop Pharm Ltda Brasil bach 62806NDcontaining 10mL) Sample B commercially available suspensions 4(produced by Smithkline Beecham Laboratory Ltda Brasil bach TLZ0246containing 10mL) and Sample C simulated Suspensions 4

Ultraviolet Spectrophotometry

A 50ml aliquot of commercially available (A and B) and simulated(C) samples equivalent to 2000mg of albendazole were transferred to a200ml volumetric flask 1000ml of 2 sulfuric acid in methanol wereadded and the solution was homogenized for 10 minutes in ultrasoundSolution A was diluted to volume and filtered 50ml of solution A weretransferred to a 100ml volumetric flask and were diluted to volume with 2sulfuric acid in methanol (solution B) 10 aliquots of 50ml of solution Bwere transferred to 10 50ml volumetric flasks and after completing thevolume with distilled water a solution with 50 mg albendazoleml concen-tration was obtained Absorbances of sample solutions were determined in230 nm using 2 sulfuric acid in methanol as a blank Quantification ofresults was made using the calibration curve

Standard Solution

One 50mL aliquot of stock solution (5000 mgmL of albendazole) wastransferred to a 100mL volumetric flask and the volume was reached with asolution of 2 sulfuric acid in methanol obtaining the 250 mgmL concen-tration solution From this solution other solutions with known concentra-tions of albendazole (25 to 75 mgmL) were prepared in distilled waterReadings of absorbances were done at 230 nm after the apparatus was cali-brated with a solution of 2 sulfuric acid in methanol used as a blankReadings were done in three repetitions

ALBENDAZOLE IN ORAL SUSPENSION 1257

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Determination of Calibration Curve

Quantification of results was done through calibration curves obtainedfrom the concentrations of the standard albendazole (25 35 45 55 6575 mgml) and respective absorbances

High Performance Liquid Chromatography (HPLC)

Chromatographic Conditions

The mobile phase is a mixture of methanol phosphate buffer005M (pH 58) (7030 vv) filtered under vacuum through a Milliporesystem filter 022 mm degaseificated with helium The column (Nucleosil

C 18 (5 m 150 460 nm) Phonomenex was kept at room temperature(20ndash25C) The flow rate was kept constant at 10mlmin The absorbanceat 254 nmwas recorded at a sensitivity of 0032 ausf and injection volume of200 ml

Stock Solutions and Standard Curve Preparation

Stock solution of albendazole (5000 mgmL) was prepared in 2 sul-furic acid in methanol Standard samples were prepared by various dilutionsof stock solutions of albendazole with mobile phase consisting of methanolphosphate buffer 005M (7030 vv) to obtain concentration between 01 mg05 mg 20 mg 50 mg 100 mg 150 mgmL Triplicate 20 mL injections weremade into the loop for each solution and the peak area ratio of albendazolewas plotted against the corresponding concentration to obtain the calibra-tion graph The standard curve was linear (r2gt0999) over the workingrange of the study

Sample Analysis

Five milliliters of commercially available (A and B) and simulated(C) suspensions equivalent to 2000mg of albendazole were quantitativelytransferred to a 200ML volumetric flask containing 500mL of formic acid1M in methanol After total dissolution helped with ultrasound for10 minutes the volume was reached with the same solution The solution wasfiltered through a 022 mm filter A solution containing 50 mgmL of albenda-zole was obtained after two subsequent dilutions of the filtered solution

1258 FREGONEZI-NERY ET AL

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ORDER REPRINTS

The albendazole and the respective concentrations expressed in mgmlwere obtained from the calibration curve Ten determinations for eachsample were done and the results were expressed in mg of albendazolemLof suspension

COMPARISON OF SPECTROPHOTOMETRIC

METHOD IN ULTRAVIOLET AND HIGH

PERFORMANCE LIQUID CHROMATOGRAPHY

Accuracy of the proposed methods was compared through varianceanalysis (ANOVA) using the Snedecor F test and the precision using StudantT test The SAS (Statistical Analyses System ndash 1997) software was used

RESULTS AND DISCUSSION

The results obtained in the standardization through the spectrophoto-metric method in ultraviolet aiming at verifying the method linearity showedthat the albendazole solutions presented linear correlation between absor-bances at 230 nm and the concentrations in the interval 25 to 75 mgmL ofalbendazole with a coefficient of correlation of 09995 (Table 1)

The results from the use of the spectrophotometric method in UV foranalysis of commercially available (A and B) and simulated (C) samples areshown in Table 2 These results showed that the method is accurate withcoefficients of variation of 073 067 and 062 for the average of tendeterminations of samples A B and C respectively

Results of albendazole recuperation in commercially available(A and B) and simulated (C) samples are shown in Table 2 The 9960 to10142 recuperation confirms the method accuracy ie there is a con-cordance between the obtained and the theoretical results

ALBENDAZOLE IN ORAL SUSPENSION 1259

Table 1 Statistical Analysis of the Determination of Albendazole by UVSpectrophotometric and High Performance Liquid Chromatography (HPLC)

Method

MethodLinear Range

(mgmL) Slope Intercept r

UV 2575 102 101 47 103 09995

HPLC 01150 75 105 204 102 09999

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The standardization of the chromatographic method for albendazole

determination showed a linear correlation with a 09999 coefficient of cor-

relation between the peak area and the 01 to 150 mgmL albendazole con-

centration (Table 1)

In Table 2 the low variation coefficients (084 175 078)

obtained by the HPLC method for analysis of commercially available

(A and B) and simulated (C) samples confirm the accuracy of this

method The method precision is also confirmed by the results obtained in

the recuperation test It can be checked in Table 3 that there was a slight

variation in percentage of recuperation 9957 to 10083 in relation to

the quantity added

Detection of interferents from the formulation excipients indicated

that they do not influence either method studied

Comparison of accuracy for both methods was made by the F test

where variance of both methods are compared By the results obtained

(Table 4) it was concluded that there is no significant difference at the 5

level between the proposed methods concerning accuracy

For comparison of precision the T test was used With this test it is

possible to assess if the averages of the experimental values of two proposed

methods UV and HLPC show significant difference at the 5 level Table 5

shows the statistical results obtained estimated from a total of 16 degrees of

freedom whose t value calculated of 11463 was lower than t tabulated of

2201 for 95 Thus the two methods do not show significant difference

concerning precision

1260 FREGONEZI-NERY ET AL

Table 2 Statistical Data Obtained in the Determination of the AlbendazoleContent in Commercially Available (A and B) and Simulated (C) Samples by theUV Spectrophotometric Method and High Performance Liquid Chromatography

Method Sample

DeclaredAmount(mg)

FoundAmount(mg)

Coefficientof Variation

()

ConfidenceLimit

Pfrac14 95

A 40000 38155 073 38155plusmn198

UV B 40000 38624 067 38624plusmn185C 40000 42110 062 42110plusmn180

A 40000 38840 084 3884plusmn232HPLC B 40000 37280 175 37280plusmn468

C 40000 42716 078 42710plusmn256

Average of 10 determinations

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ORDER REPRINTS

CONCLUSION

The methods proposed for determination of albendazole in oral sus-pension showed linear correlation were accurate exact and did not show

ALBENDAZOLE IN ORAL SUSPENSION 1261

Table 4 Experimental Data obtained from Analysis of Variance (ANOVA) WhenComparing Accuracy of Methods UV and HPLC

Resons forVariation

Degree ofLiberty Square Sum Square Mean F PrgtF

Sample 2 162214 81107 57030 00001Treatment 1 063 063 044 05075

Error 56 7964 14Total 59 170241

Table 3 Results of Albendazole Recuperation of Commercially Available (A andB) and Simulated (C) Samples by the UV Spectrophotometric Method and HighPerformance Liquid Chromatography

Method Sample Added (mg) Found (mg) Recovery ()

250 251 10040A 350 352 10057

450 455 10110

250 250 10000UV B 350 349 9971

450 451 10020

250 252 10080C 350 355 10140

450 448 9960

500 498 9960A 600 605 10083

700 703 10043

500 501 10020HPLC B 600 599 9933

700 697 9957

500 500 10000C 600 603 10050

700 701 10014

Average of 2 determinations

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ORDER REPRINTS

significant statistical difference concerning accuracy nor exactness

Therefore it is possible to use either of the two methods for the analysis

of albendazole in oral suspensions and the choice will depend on method

cost and benefit

REFERENCES

1 Barragry T Anthelmintics a review N Z Vet J 1984 32 161ndash164

2 CookGCUse of benzimidazole chemotherapy in human helminthiases

indications and efficacy Parasitol Today 1990 6(4) 133ndash136

3 Coulaud JP Rossingnol JF Albendazole a new single dose anthel-

mintic Acta Trop 1984 45 87ndash90

4 Gasparine EA Atualizac ao em parasitoses intestinais J Bras Med

1995 68 (4)

5 Bandres JC Clinton White A Jr Samo T Murphy EC Harris

RL Extraparenchymal neurocysticercosis Report of five cases andreview of management Clin Infect Dis 1992 15 799ndash811

6 Alvinerie M Galtier P Simultaneous determination of albendazole

and its principal metabolites in plasma by normal phase high-

performance liquid chromatography J Pharm Biomed Anal 1984

2 73ndash79

7 Bogan JA Marriner S Analysis of benzimidazoles in body fluids by

high-performance liquid chromatography J Pharm Sci 1980 69

422ndash423

8 Hoaksey PE Awadzi K Ward SA Conventry PA Orne MLE

Edwards G Rapid and sensitive method for the determination of alben-

dazole sulphoxide in biological fluids J Chromatogr 1991 566(1)

244ndash249

1262 FREGONEZI-NERY ET AL

Table 5 Results Obtained When Comparing Accuracy ofProposed Methods Using the t Test

Parameters UV HPLC

x 10042 10012

S 061 047n 10 10

Ttabulated for 16 degrees of liberty (Pfrac14 95)frac14 20101

Tcalculated frac14 11463 xxfrac14Mean of experimental values ()S frac14 Standard deviation nfrac14Number of determinations

Dow

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ded

by [

The

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ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

ORDER REPRINTS

9 Hurtado M Medina MT Sotelo J Jung H Sensitive high

performance liquid chromatographic assay for albendazole and its

main metabolite albendazole sulphoxid in plasma and cerebrospinal

fluid J Chromatogr 1989 494 403ndash407

10 Meulemans A Giovangeli MD Mohler J Vulpillat M Hay

JM Saimot AG High performance liquid chromatography of

albendazol and its sulfoxide metabolite in human organs and fluids

during hydatidosis J Liq Chromatog 1984 7 569ndash580

11 Zeugin T Sysset T Cotting J Therapeutic monitoring of albenda-

zole a high performance liquid chromatography method for determi-

nation of its active metabolite albendazole sulfoxid Ther Drug Monit

1990 12 187ndash190

12 Bergold AM Korolkovas A Doseamento do albendazol como

materia prima e em comprimidos em meio nao aquoso com acido

perclorico Rev Farm Bioquim S Paulo 1993 29(1) 31ndash34

13 Laurentis N Milillo MA Bruno S Determination of albendazole

as raw material and in tablets by nonaqueous tituration with sodium

methylate solution Rev Farm Bioquim S Paulo 1997 33(1) 23ndash27

14 Long AR Hsieh LC Short CR Barker SA Isocratic liquid

chromatographywith photodiode array characterization JChromatogr

1989 475 404ndash411

15 Mandal SC Bhattacharyya M Maity AK Gupta BK Ghosal

SKL Determination of albendazole in tablet formulations by UV

spectrophotometric method Indian Drugs 1992 29(7) 323ndash324

16 Sane RT Samant RS Joshi MD Purandare SM Tembe PB

Nayak VG High performance liquid chromatographic determination

of albendazole in pharmaceuticals Indian Drugs 1989 26 494ndash496

17 United States pharmacopeia 23 ed Rockiville United States

Pharmacopeial Convention 1995 37ndash38 1957ndash1963

18 Dicionario de especialidades farmaceuticas 26 ed Rio de Janeiro

Publicac oes Cientıficas 19971998

Received July 31 2000

Accepted February 13 2001

ALBENDAZOLE IN ORAL SUSPENSION 1263

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Order now

Reprints of this article can also be ordered at

httpwwwdekkercomservletproductDOI101081AL100104151

Request Permission or Order Reprints Instantly

Interested in copying and sharing this article In most cases US Copyright Law requires that you get permission from the articlersquos rightsholder before using copyrighted content

All information and materials found in this article including but not limited to text trademarks patents logos graphics and images (the Materials) are the copyrighted works and other forms of intellectual property of Marcel Dekker Inc or its licensors All rights not expressly granted are reserved

Get permission to lawfully reproduce and distribute the Materials or order reprints quickly and painlessly Simply click on the Request PermissionReprints Here link below and follow the instructions Visit the US Copyright Office for information on Fair Use limitations of US copyright law Please refer to The Association of American Publishersrsquo (AAP) website for guidelines on Fair Use in the Classroom

The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

Dow

nloa

ded

by [

The

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vers

ity o

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anch

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Page 4: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION

ORDER REPRINTS

ultraviolet detector The detector was set at 254 nm Test samples wereinjected using a model 7725 Rheodyne valve with a 20 mL loop and peakareas were integrated automatically by computer For the UV Spectro-photometer Shimadzu ndash model UV-160A was used

Samples

The samples used were Sample A commercially available suspensions4 (produced by Sanfi Winthrop Pharm Ltda Brasil bach 62806NDcontaining 10mL) Sample B commercially available suspensions 4(produced by Smithkline Beecham Laboratory Ltda Brasil bach TLZ0246containing 10mL) and Sample C simulated Suspensions 4

Ultraviolet Spectrophotometry

A 50ml aliquot of commercially available (A and B) and simulated(C) samples equivalent to 2000mg of albendazole were transferred to a200ml volumetric flask 1000ml of 2 sulfuric acid in methanol wereadded and the solution was homogenized for 10 minutes in ultrasoundSolution A was diluted to volume and filtered 50ml of solution A weretransferred to a 100ml volumetric flask and were diluted to volume with 2sulfuric acid in methanol (solution B) 10 aliquots of 50ml of solution Bwere transferred to 10 50ml volumetric flasks and after completing thevolume with distilled water a solution with 50 mg albendazoleml concen-tration was obtained Absorbances of sample solutions were determined in230 nm using 2 sulfuric acid in methanol as a blank Quantification ofresults was made using the calibration curve

Standard Solution

One 50mL aliquot of stock solution (5000 mgmL of albendazole) wastransferred to a 100mL volumetric flask and the volume was reached with asolution of 2 sulfuric acid in methanol obtaining the 250 mgmL concen-tration solution From this solution other solutions with known concentra-tions of albendazole (25 to 75 mgmL) were prepared in distilled waterReadings of absorbances were done at 230 nm after the apparatus was cali-brated with a solution of 2 sulfuric acid in methanol used as a blankReadings were done in three repetitions

ALBENDAZOLE IN ORAL SUSPENSION 1257

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ORDER REPRINTS

Determination of Calibration Curve

Quantification of results was done through calibration curves obtainedfrom the concentrations of the standard albendazole (25 35 45 55 6575 mgml) and respective absorbances

High Performance Liquid Chromatography (HPLC)

Chromatographic Conditions

The mobile phase is a mixture of methanol phosphate buffer005M (pH 58) (7030 vv) filtered under vacuum through a Milliporesystem filter 022 mm degaseificated with helium The column (Nucleosil

C 18 (5 m 150 460 nm) Phonomenex was kept at room temperature(20ndash25C) The flow rate was kept constant at 10mlmin The absorbanceat 254 nmwas recorded at a sensitivity of 0032 ausf and injection volume of200 ml

Stock Solutions and Standard Curve Preparation

Stock solution of albendazole (5000 mgmL) was prepared in 2 sul-furic acid in methanol Standard samples were prepared by various dilutionsof stock solutions of albendazole with mobile phase consisting of methanolphosphate buffer 005M (7030 vv) to obtain concentration between 01 mg05 mg 20 mg 50 mg 100 mg 150 mgmL Triplicate 20 mL injections weremade into the loop for each solution and the peak area ratio of albendazolewas plotted against the corresponding concentration to obtain the calibra-tion graph The standard curve was linear (r2gt0999) over the workingrange of the study

Sample Analysis

Five milliliters of commercially available (A and B) and simulated(C) suspensions equivalent to 2000mg of albendazole were quantitativelytransferred to a 200ML volumetric flask containing 500mL of formic acid1M in methanol After total dissolution helped with ultrasound for10 minutes the volume was reached with the same solution The solution wasfiltered through a 022 mm filter A solution containing 50 mgmL of albenda-zole was obtained after two subsequent dilutions of the filtered solution

1258 FREGONEZI-NERY ET AL

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ORDER REPRINTS

The albendazole and the respective concentrations expressed in mgmlwere obtained from the calibration curve Ten determinations for eachsample were done and the results were expressed in mg of albendazolemLof suspension

COMPARISON OF SPECTROPHOTOMETRIC

METHOD IN ULTRAVIOLET AND HIGH

PERFORMANCE LIQUID CHROMATOGRAPHY

Accuracy of the proposed methods was compared through varianceanalysis (ANOVA) using the Snedecor F test and the precision using StudantT test The SAS (Statistical Analyses System ndash 1997) software was used

RESULTS AND DISCUSSION

The results obtained in the standardization through the spectrophoto-metric method in ultraviolet aiming at verifying the method linearity showedthat the albendazole solutions presented linear correlation between absor-bances at 230 nm and the concentrations in the interval 25 to 75 mgmL ofalbendazole with a coefficient of correlation of 09995 (Table 1)

The results from the use of the spectrophotometric method in UV foranalysis of commercially available (A and B) and simulated (C) samples areshown in Table 2 These results showed that the method is accurate withcoefficients of variation of 073 067 and 062 for the average of tendeterminations of samples A B and C respectively

Results of albendazole recuperation in commercially available(A and B) and simulated (C) samples are shown in Table 2 The 9960 to10142 recuperation confirms the method accuracy ie there is a con-cordance between the obtained and the theoretical results

ALBENDAZOLE IN ORAL SUSPENSION 1259

Table 1 Statistical Analysis of the Determination of Albendazole by UVSpectrophotometric and High Performance Liquid Chromatography (HPLC)

Method

MethodLinear Range

(mgmL) Slope Intercept r

UV 2575 102 101 47 103 09995

HPLC 01150 75 105 204 102 09999

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The standardization of the chromatographic method for albendazole

determination showed a linear correlation with a 09999 coefficient of cor-

relation between the peak area and the 01 to 150 mgmL albendazole con-

centration (Table 1)

In Table 2 the low variation coefficients (084 175 078)

obtained by the HPLC method for analysis of commercially available

(A and B) and simulated (C) samples confirm the accuracy of this

method The method precision is also confirmed by the results obtained in

the recuperation test It can be checked in Table 3 that there was a slight

variation in percentage of recuperation 9957 to 10083 in relation to

the quantity added

Detection of interferents from the formulation excipients indicated

that they do not influence either method studied

Comparison of accuracy for both methods was made by the F test

where variance of both methods are compared By the results obtained

(Table 4) it was concluded that there is no significant difference at the 5

level between the proposed methods concerning accuracy

For comparison of precision the T test was used With this test it is

possible to assess if the averages of the experimental values of two proposed

methods UV and HLPC show significant difference at the 5 level Table 5

shows the statistical results obtained estimated from a total of 16 degrees of

freedom whose t value calculated of 11463 was lower than t tabulated of

2201 for 95 Thus the two methods do not show significant difference

concerning precision

1260 FREGONEZI-NERY ET AL

Table 2 Statistical Data Obtained in the Determination of the AlbendazoleContent in Commercially Available (A and B) and Simulated (C) Samples by theUV Spectrophotometric Method and High Performance Liquid Chromatography

Method Sample

DeclaredAmount(mg)

FoundAmount(mg)

Coefficientof Variation

()

ConfidenceLimit

Pfrac14 95

A 40000 38155 073 38155plusmn198

UV B 40000 38624 067 38624plusmn185C 40000 42110 062 42110plusmn180

A 40000 38840 084 3884plusmn232HPLC B 40000 37280 175 37280plusmn468

C 40000 42716 078 42710plusmn256

Average of 10 determinations

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CONCLUSION

The methods proposed for determination of albendazole in oral sus-pension showed linear correlation were accurate exact and did not show

ALBENDAZOLE IN ORAL SUSPENSION 1261

Table 4 Experimental Data obtained from Analysis of Variance (ANOVA) WhenComparing Accuracy of Methods UV and HPLC

Resons forVariation

Degree ofLiberty Square Sum Square Mean F PrgtF

Sample 2 162214 81107 57030 00001Treatment 1 063 063 044 05075

Error 56 7964 14Total 59 170241

Table 3 Results of Albendazole Recuperation of Commercially Available (A andB) and Simulated (C) Samples by the UV Spectrophotometric Method and HighPerformance Liquid Chromatography

Method Sample Added (mg) Found (mg) Recovery ()

250 251 10040A 350 352 10057

450 455 10110

250 250 10000UV B 350 349 9971

450 451 10020

250 252 10080C 350 355 10140

450 448 9960

500 498 9960A 600 605 10083

700 703 10043

500 501 10020HPLC B 600 599 9933

700 697 9957

500 500 10000C 600 603 10050

700 701 10014

Average of 2 determinations

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ORDER REPRINTS

significant statistical difference concerning accuracy nor exactness

Therefore it is possible to use either of the two methods for the analysis

of albendazole in oral suspensions and the choice will depend on method

cost and benefit

REFERENCES

1 Barragry T Anthelmintics a review N Z Vet J 1984 32 161ndash164

2 CookGCUse of benzimidazole chemotherapy in human helminthiases

indications and efficacy Parasitol Today 1990 6(4) 133ndash136

3 Coulaud JP Rossingnol JF Albendazole a new single dose anthel-

mintic Acta Trop 1984 45 87ndash90

4 Gasparine EA Atualizac ao em parasitoses intestinais J Bras Med

1995 68 (4)

5 Bandres JC Clinton White A Jr Samo T Murphy EC Harris

RL Extraparenchymal neurocysticercosis Report of five cases andreview of management Clin Infect Dis 1992 15 799ndash811

6 Alvinerie M Galtier P Simultaneous determination of albendazole

and its principal metabolites in plasma by normal phase high-

performance liquid chromatography J Pharm Biomed Anal 1984

2 73ndash79

7 Bogan JA Marriner S Analysis of benzimidazoles in body fluids by

high-performance liquid chromatography J Pharm Sci 1980 69

422ndash423

8 Hoaksey PE Awadzi K Ward SA Conventry PA Orne MLE

Edwards G Rapid and sensitive method for the determination of alben-

dazole sulphoxide in biological fluids J Chromatogr 1991 566(1)

244ndash249

1262 FREGONEZI-NERY ET AL

Table 5 Results Obtained When Comparing Accuracy ofProposed Methods Using the t Test

Parameters UV HPLC

x 10042 10012

S 061 047n 10 10

Ttabulated for 16 degrees of liberty (Pfrac14 95)frac14 20101

Tcalculated frac14 11463 xxfrac14Mean of experimental values ()S frac14 Standard deviation nfrac14Number of determinations

Dow

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ded

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vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

ORDER REPRINTS

9 Hurtado M Medina MT Sotelo J Jung H Sensitive high

performance liquid chromatographic assay for albendazole and its

main metabolite albendazole sulphoxid in plasma and cerebrospinal

fluid J Chromatogr 1989 494 403ndash407

10 Meulemans A Giovangeli MD Mohler J Vulpillat M Hay

JM Saimot AG High performance liquid chromatography of

albendazol and its sulfoxide metabolite in human organs and fluids

during hydatidosis J Liq Chromatog 1984 7 569ndash580

11 Zeugin T Sysset T Cotting J Therapeutic monitoring of albenda-

zole a high performance liquid chromatography method for determi-

nation of its active metabolite albendazole sulfoxid Ther Drug Monit

1990 12 187ndash190

12 Bergold AM Korolkovas A Doseamento do albendazol como

materia prima e em comprimidos em meio nao aquoso com acido

perclorico Rev Farm Bioquim S Paulo 1993 29(1) 31ndash34

13 Laurentis N Milillo MA Bruno S Determination of albendazole

as raw material and in tablets by nonaqueous tituration with sodium

methylate solution Rev Farm Bioquim S Paulo 1997 33(1) 23ndash27

14 Long AR Hsieh LC Short CR Barker SA Isocratic liquid

chromatographywith photodiode array characterization JChromatogr

1989 475 404ndash411

15 Mandal SC Bhattacharyya M Maity AK Gupta BK Ghosal

SKL Determination of albendazole in tablet formulations by UV

spectrophotometric method Indian Drugs 1992 29(7) 323ndash324

16 Sane RT Samant RS Joshi MD Purandare SM Tembe PB

Nayak VG High performance liquid chromatographic determination

of albendazole in pharmaceuticals Indian Drugs 1989 26 494ndash496

17 United States pharmacopeia 23 ed Rockiville United States

Pharmacopeial Convention 1995 37ndash38 1957ndash1963

18 Dicionario de especialidades farmaceuticas 26 ed Rio de Janeiro

Publicac oes Cientıficas 19971998

Received July 31 2000

Accepted February 13 2001

ALBENDAZOLE IN ORAL SUSPENSION 1263

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embe

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Order now

Reprints of this article can also be ordered at

httpwwwdekkercomservletproductDOI101081AL100104151

Request Permission or Order Reprints Instantly

Interested in copying and sharing this article In most cases US Copyright Law requires that you get permission from the articlersquos rightsholder before using copyrighted content

All information and materials found in this article including but not limited to text trademarks patents logos graphics and images (the Materials) are the copyrighted works and other forms of intellectual property of Marcel Dekker Inc or its licensors All rights not expressly granted are reserved

Get permission to lawfully reproduce and distribute the Materials or order reprints quickly and painlessly Simply click on the Request PermissionReprints Here link below and follow the instructions Visit the US Copyright Office for information on Fair Use limitations of US copyright law Please refer to The Association of American Publishersrsquo (AAP) website for guidelines on Fair Use in the Classroom

The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

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Page 5: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION

ORDER REPRINTS

Determination of Calibration Curve

Quantification of results was done through calibration curves obtainedfrom the concentrations of the standard albendazole (25 35 45 55 6575 mgml) and respective absorbances

High Performance Liquid Chromatography (HPLC)

Chromatographic Conditions

The mobile phase is a mixture of methanol phosphate buffer005M (pH 58) (7030 vv) filtered under vacuum through a Milliporesystem filter 022 mm degaseificated with helium The column (Nucleosil

C 18 (5 m 150 460 nm) Phonomenex was kept at room temperature(20ndash25C) The flow rate was kept constant at 10mlmin The absorbanceat 254 nmwas recorded at a sensitivity of 0032 ausf and injection volume of200 ml

Stock Solutions and Standard Curve Preparation

Stock solution of albendazole (5000 mgmL) was prepared in 2 sul-furic acid in methanol Standard samples were prepared by various dilutionsof stock solutions of albendazole with mobile phase consisting of methanolphosphate buffer 005M (7030 vv) to obtain concentration between 01 mg05 mg 20 mg 50 mg 100 mg 150 mgmL Triplicate 20 mL injections weremade into the loop for each solution and the peak area ratio of albendazolewas plotted against the corresponding concentration to obtain the calibra-tion graph The standard curve was linear (r2gt0999) over the workingrange of the study

Sample Analysis

Five milliliters of commercially available (A and B) and simulated(C) suspensions equivalent to 2000mg of albendazole were quantitativelytransferred to a 200ML volumetric flask containing 500mL of formic acid1M in methanol After total dissolution helped with ultrasound for10 minutes the volume was reached with the same solution The solution wasfiltered through a 022 mm filter A solution containing 50 mgmL of albenda-zole was obtained after two subsequent dilutions of the filtered solution

1258 FREGONEZI-NERY ET AL

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este

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ry]

at 2

003

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Dec

embe

r 20

14

ORDER REPRINTS

The albendazole and the respective concentrations expressed in mgmlwere obtained from the calibration curve Ten determinations for eachsample were done and the results were expressed in mg of albendazolemLof suspension

COMPARISON OF SPECTROPHOTOMETRIC

METHOD IN ULTRAVIOLET AND HIGH

PERFORMANCE LIQUID CHROMATOGRAPHY

Accuracy of the proposed methods was compared through varianceanalysis (ANOVA) using the Snedecor F test and the precision using StudantT test The SAS (Statistical Analyses System ndash 1997) software was used

RESULTS AND DISCUSSION

The results obtained in the standardization through the spectrophoto-metric method in ultraviolet aiming at verifying the method linearity showedthat the albendazole solutions presented linear correlation between absor-bances at 230 nm and the concentrations in the interval 25 to 75 mgmL ofalbendazole with a coefficient of correlation of 09995 (Table 1)

The results from the use of the spectrophotometric method in UV foranalysis of commercially available (A and B) and simulated (C) samples areshown in Table 2 These results showed that the method is accurate withcoefficients of variation of 073 067 and 062 for the average of tendeterminations of samples A B and C respectively

Results of albendazole recuperation in commercially available(A and B) and simulated (C) samples are shown in Table 2 The 9960 to10142 recuperation confirms the method accuracy ie there is a con-cordance between the obtained and the theoretical results

ALBENDAZOLE IN ORAL SUSPENSION 1259

Table 1 Statistical Analysis of the Determination of Albendazole by UVSpectrophotometric and High Performance Liquid Chromatography (HPLC)

Method

MethodLinear Range

(mgmL) Slope Intercept r

UV 2575 102 101 47 103 09995

HPLC 01150 75 105 204 102 09999

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embe

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14

ORDER REPRINTS

The standardization of the chromatographic method for albendazole

determination showed a linear correlation with a 09999 coefficient of cor-

relation between the peak area and the 01 to 150 mgmL albendazole con-

centration (Table 1)

In Table 2 the low variation coefficients (084 175 078)

obtained by the HPLC method for analysis of commercially available

(A and B) and simulated (C) samples confirm the accuracy of this

method The method precision is also confirmed by the results obtained in

the recuperation test It can be checked in Table 3 that there was a slight

variation in percentage of recuperation 9957 to 10083 in relation to

the quantity added

Detection of interferents from the formulation excipients indicated

that they do not influence either method studied

Comparison of accuracy for both methods was made by the F test

where variance of both methods are compared By the results obtained

(Table 4) it was concluded that there is no significant difference at the 5

level between the proposed methods concerning accuracy

For comparison of precision the T test was used With this test it is

possible to assess if the averages of the experimental values of two proposed

methods UV and HLPC show significant difference at the 5 level Table 5

shows the statistical results obtained estimated from a total of 16 degrees of

freedom whose t value calculated of 11463 was lower than t tabulated of

2201 for 95 Thus the two methods do not show significant difference

concerning precision

1260 FREGONEZI-NERY ET AL

Table 2 Statistical Data Obtained in the Determination of the AlbendazoleContent in Commercially Available (A and B) and Simulated (C) Samples by theUV Spectrophotometric Method and High Performance Liquid Chromatography

Method Sample

DeclaredAmount(mg)

FoundAmount(mg)

Coefficientof Variation

()

ConfidenceLimit

Pfrac14 95

A 40000 38155 073 38155plusmn198

UV B 40000 38624 067 38624plusmn185C 40000 42110 062 42110plusmn180

A 40000 38840 084 3884plusmn232HPLC B 40000 37280 175 37280plusmn468

C 40000 42716 078 42710plusmn256

Average of 10 determinations

Dow

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ded

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ry]

at 2

003

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Dec

embe

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14

ORDER REPRINTS

CONCLUSION

The methods proposed for determination of albendazole in oral sus-pension showed linear correlation were accurate exact and did not show

ALBENDAZOLE IN ORAL SUSPENSION 1261

Table 4 Experimental Data obtained from Analysis of Variance (ANOVA) WhenComparing Accuracy of Methods UV and HPLC

Resons forVariation

Degree ofLiberty Square Sum Square Mean F PrgtF

Sample 2 162214 81107 57030 00001Treatment 1 063 063 044 05075

Error 56 7964 14Total 59 170241

Table 3 Results of Albendazole Recuperation of Commercially Available (A andB) and Simulated (C) Samples by the UV Spectrophotometric Method and HighPerformance Liquid Chromatography

Method Sample Added (mg) Found (mg) Recovery ()

250 251 10040A 350 352 10057

450 455 10110

250 250 10000UV B 350 349 9971

450 451 10020

250 252 10080C 350 355 10140

450 448 9960

500 498 9960A 600 605 10083

700 703 10043

500 501 10020HPLC B 600 599 9933

700 697 9957

500 500 10000C 600 603 10050

700 701 10014

Average of 2 determinations

Dow

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ded

by [

The

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f M

anch

este

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ry]

at 2

003

19

Dec

embe

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14

ORDER REPRINTS

significant statistical difference concerning accuracy nor exactness

Therefore it is possible to use either of the two methods for the analysis

of albendazole in oral suspensions and the choice will depend on method

cost and benefit

REFERENCES

1 Barragry T Anthelmintics a review N Z Vet J 1984 32 161ndash164

2 CookGCUse of benzimidazole chemotherapy in human helminthiases

indications and efficacy Parasitol Today 1990 6(4) 133ndash136

3 Coulaud JP Rossingnol JF Albendazole a new single dose anthel-

mintic Acta Trop 1984 45 87ndash90

4 Gasparine EA Atualizac ao em parasitoses intestinais J Bras Med

1995 68 (4)

5 Bandres JC Clinton White A Jr Samo T Murphy EC Harris

RL Extraparenchymal neurocysticercosis Report of five cases andreview of management Clin Infect Dis 1992 15 799ndash811

6 Alvinerie M Galtier P Simultaneous determination of albendazole

and its principal metabolites in plasma by normal phase high-

performance liquid chromatography J Pharm Biomed Anal 1984

2 73ndash79

7 Bogan JA Marriner S Analysis of benzimidazoles in body fluids by

high-performance liquid chromatography J Pharm Sci 1980 69

422ndash423

8 Hoaksey PE Awadzi K Ward SA Conventry PA Orne MLE

Edwards G Rapid and sensitive method for the determination of alben-

dazole sulphoxide in biological fluids J Chromatogr 1991 566(1)

244ndash249

1262 FREGONEZI-NERY ET AL

Table 5 Results Obtained When Comparing Accuracy ofProposed Methods Using the t Test

Parameters UV HPLC

x 10042 10012

S 061 047n 10 10

Ttabulated for 16 degrees of liberty (Pfrac14 95)frac14 20101

Tcalculated frac14 11463 xxfrac14Mean of experimental values ()S frac14 Standard deviation nfrac14Number of determinations

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

ORDER REPRINTS

9 Hurtado M Medina MT Sotelo J Jung H Sensitive high

performance liquid chromatographic assay for albendazole and its

main metabolite albendazole sulphoxid in plasma and cerebrospinal

fluid J Chromatogr 1989 494 403ndash407

10 Meulemans A Giovangeli MD Mohler J Vulpillat M Hay

JM Saimot AG High performance liquid chromatography of

albendazol and its sulfoxide metabolite in human organs and fluids

during hydatidosis J Liq Chromatog 1984 7 569ndash580

11 Zeugin T Sysset T Cotting J Therapeutic monitoring of albenda-

zole a high performance liquid chromatography method for determi-

nation of its active metabolite albendazole sulfoxid Ther Drug Monit

1990 12 187ndash190

12 Bergold AM Korolkovas A Doseamento do albendazol como

materia prima e em comprimidos em meio nao aquoso com acido

perclorico Rev Farm Bioquim S Paulo 1993 29(1) 31ndash34

13 Laurentis N Milillo MA Bruno S Determination of albendazole

as raw material and in tablets by nonaqueous tituration with sodium

methylate solution Rev Farm Bioquim S Paulo 1997 33(1) 23ndash27

14 Long AR Hsieh LC Short CR Barker SA Isocratic liquid

chromatographywith photodiode array characterization JChromatogr

1989 475 404ndash411

15 Mandal SC Bhattacharyya M Maity AK Gupta BK Ghosal

SKL Determination of albendazole in tablet formulations by UV

spectrophotometric method Indian Drugs 1992 29(7) 323ndash324

16 Sane RT Samant RS Joshi MD Purandare SM Tembe PB

Nayak VG High performance liquid chromatographic determination

of albendazole in pharmaceuticals Indian Drugs 1989 26 494ndash496

17 United States pharmacopeia 23 ed Rockiville United States

Pharmacopeial Convention 1995 37ndash38 1957ndash1963

18 Dicionario de especialidades farmaceuticas 26 ed Rio de Janeiro

Publicac oes Cientıficas 19971998

Received July 31 2000

Accepted February 13 2001

ALBENDAZOLE IN ORAL SUSPENSION 1263

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

Order now

Reprints of this article can also be ordered at

httpwwwdekkercomservletproductDOI101081AL100104151

Request Permission or Order Reprints Instantly

Interested in copying and sharing this article In most cases US Copyright Law requires that you get permission from the articlersquos rightsholder before using copyrighted content

All information and materials found in this article including but not limited to text trademarks patents logos graphics and images (the Materials) are the copyrighted works and other forms of intellectual property of Marcel Dekker Inc or its licensors All rights not expressly granted are reserved

Get permission to lawfully reproduce and distribute the Materials or order reprints quickly and painlessly Simply click on the Request PermissionReprints Here link below and follow the instructions Visit the US Copyright Office for information on Fair Use limitations of US copyright law Please refer to The Association of American Publishersrsquo (AAP) website for guidelines on Fair Use in the Classroom

The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

Page 6: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION

ORDER REPRINTS

The albendazole and the respective concentrations expressed in mgmlwere obtained from the calibration curve Ten determinations for eachsample were done and the results were expressed in mg of albendazolemLof suspension

COMPARISON OF SPECTROPHOTOMETRIC

METHOD IN ULTRAVIOLET AND HIGH

PERFORMANCE LIQUID CHROMATOGRAPHY

Accuracy of the proposed methods was compared through varianceanalysis (ANOVA) using the Snedecor F test and the precision using StudantT test The SAS (Statistical Analyses System ndash 1997) software was used

RESULTS AND DISCUSSION

The results obtained in the standardization through the spectrophoto-metric method in ultraviolet aiming at verifying the method linearity showedthat the albendazole solutions presented linear correlation between absor-bances at 230 nm and the concentrations in the interval 25 to 75 mgmL ofalbendazole with a coefficient of correlation of 09995 (Table 1)

The results from the use of the spectrophotometric method in UV foranalysis of commercially available (A and B) and simulated (C) samples areshown in Table 2 These results showed that the method is accurate withcoefficients of variation of 073 067 and 062 for the average of tendeterminations of samples A B and C respectively

Results of albendazole recuperation in commercially available(A and B) and simulated (C) samples are shown in Table 2 The 9960 to10142 recuperation confirms the method accuracy ie there is a con-cordance between the obtained and the theoretical results

ALBENDAZOLE IN ORAL SUSPENSION 1259

Table 1 Statistical Analysis of the Determination of Albendazole by UVSpectrophotometric and High Performance Liquid Chromatography (HPLC)

Method

MethodLinear Range

(mgmL) Slope Intercept r

UV 2575 102 101 47 103 09995

HPLC 01150 75 105 204 102 09999

Dow

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ded

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vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

ORDER REPRINTS

The standardization of the chromatographic method for albendazole

determination showed a linear correlation with a 09999 coefficient of cor-

relation between the peak area and the 01 to 150 mgmL albendazole con-

centration (Table 1)

In Table 2 the low variation coefficients (084 175 078)

obtained by the HPLC method for analysis of commercially available

(A and B) and simulated (C) samples confirm the accuracy of this

method The method precision is also confirmed by the results obtained in

the recuperation test It can be checked in Table 3 that there was a slight

variation in percentage of recuperation 9957 to 10083 in relation to

the quantity added

Detection of interferents from the formulation excipients indicated

that they do not influence either method studied

Comparison of accuracy for both methods was made by the F test

where variance of both methods are compared By the results obtained

(Table 4) it was concluded that there is no significant difference at the 5

level between the proposed methods concerning accuracy

For comparison of precision the T test was used With this test it is

possible to assess if the averages of the experimental values of two proposed

methods UV and HLPC show significant difference at the 5 level Table 5

shows the statistical results obtained estimated from a total of 16 degrees of

freedom whose t value calculated of 11463 was lower than t tabulated of

2201 for 95 Thus the two methods do not show significant difference

concerning precision

1260 FREGONEZI-NERY ET AL

Table 2 Statistical Data Obtained in the Determination of the AlbendazoleContent in Commercially Available (A and B) and Simulated (C) Samples by theUV Spectrophotometric Method and High Performance Liquid Chromatography

Method Sample

DeclaredAmount(mg)

FoundAmount(mg)

Coefficientof Variation

()

ConfidenceLimit

Pfrac14 95

A 40000 38155 073 38155plusmn198

UV B 40000 38624 067 38624plusmn185C 40000 42110 062 42110plusmn180

A 40000 38840 084 3884plusmn232HPLC B 40000 37280 175 37280plusmn468

C 40000 42716 078 42710plusmn256

Average of 10 determinations

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

ORDER REPRINTS

CONCLUSION

The methods proposed for determination of albendazole in oral sus-pension showed linear correlation were accurate exact and did not show

ALBENDAZOLE IN ORAL SUSPENSION 1261

Table 4 Experimental Data obtained from Analysis of Variance (ANOVA) WhenComparing Accuracy of Methods UV and HPLC

Resons forVariation

Degree ofLiberty Square Sum Square Mean F PrgtF

Sample 2 162214 81107 57030 00001Treatment 1 063 063 044 05075

Error 56 7964 14Total 59 170241

Table 3 Results of Albendazole Recuperation of Commercially Available (A andB) and Simulated (C) Samples by the UV Spectrophotometric Method and HighPerformance Liquid Chromatography

Method Sample Added (mg) Found (mg) Recovery ()

250 251 10040A 350 352 10057

450 455 10110

250 250 10000UV B 350 349 9971

450 451 10020

250 252 10080C 350 355 10140

450 448 9960

500 498 9960A 600 605 10083

700 703 10043

500 501 10020HPLC B 600 599 9933

700 697 9957

500 500 10000C 600 603 10050

700 701 10014

Average of 2 determinations

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

ORDER REPRINTS

significant statistical difference concerning accuracy nor exactness

Therefore it is possible to use either of the two methods for the analysis

of albendazole in oral suspensions and the choice will depend on method

cost and benefit

REFERENCES

1 Barragry T Anthelmintics a review N Z Vet J 1984 32 161ndash164

2 CookGCUse of benzimidazole chemotherapy in human helminthiases

indications and efficacy Parasitol Today 1990 6(4) 133ndash136

3 Coulaud JP Rossingnol JF Albendazole a new single dose anthel-

mintic Acta Trop 1984 45 87ndash90

4 Gasparine EA Atualizac ao em parasitoses intestinais J Bras Med

1995 68 (4)

5 Bandres JC Clinton White A Jr Samo T Murphy EC Harris

RL Extraparenchymal neurocysticercosis Report of five cases andreview of management Clin Infect Dis 1992 15 799ndash811

6 Alvinerie M Galtier P Simultaneous determination of albendazole

and its principal metabolites in plasma by normal phase high-

performance liquid chromatography J Pharm Biomed Anal 1984

2 73ndash79

7 Bogan JA Marriner S Analysis of benzimidazoles in body fluids by

high-performance liquid chromatography J Pharm Sci 1980 69

422ndash423

8 Hoaksey PE Awadzi K Ward SA Conventry PA Orne MLE

Edwards G Rapid and sensitive method for the determination of alben-

dazole sulphoxide in biological fluids J Chromatogr 1991 566(1)

244ndash249

1262 FREGONEZI-NERY ET AL

Table 5 Results Obtained When Comparing Accuracy ofProposed Methods Using the t Test

Parameters UV HPLC

x 10042 10012

S 061 047n 10 10

Ttabulated for 16 degrees of liberty (Pfrac14 95)frac14 20101

Tcalculated frac14 11463 xxfrac14Mean of experimental values ()S frac14 Standard deviation nfrac14Number of determinations

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

ORDER REPRINTS

9 Hurtado M Medina MT Sotelo J Jung H Sensitive high

performance liquid chromatographic assay for albendazole and its

main metabolite albendazole sulphoxid in plasma and cerebrospinal

fluid J Chromatogr 1989 494 403ndash407

10 Meulemans A Giovangeli MD Mohler J Vulpillat M Hay

JM Saimot AG High performance liquid chromatography of

albendazol and its sulfoxide metabolite in human organs and fluids

during hydatidosis J Liq Chromatog 1984 7 569ndash580

11 Zeugin T Sysset T Cotting J Therapeutic monitoring of albenda-

zole a high performance liquid chromatography method for determi-

nation of its active metabolite albendazole sulfoxid Ther Drug Monit

1990 12 187ndash190

12 Bergold AM Korolkovas A Doseamento do albendazol como

materia prima e em comprimidos em meio nao aquoso com acido

perclorico Rev Farm Bioquim S Paulo 1993 29(1) 31ndash34

13 Laurentis N Milillo MA Bruno S Determination of albendazole

as raw material and in tablets by nonaqueous tituration with sodium

methylate solution Rev Farm Bioquim S Paulo 1997 33(1) 23ndash27

14 Long AR Hsieh LC Short CR Barker SA Isocratic liquid

chromatographywith photodiode array characterization JChromatogr

1989 475 404ndash411

15 Mandal SC Bhattacharyya M Maity AK Gupta BK Ghosal

SKL Determination of albendazole in tablet formulations by UV

spectrophotometric method Indian Drugs 1992 29(7) 323ndash324

16 Sane RT Samant RS Joshi MD Purandare SM Tembe PB

Nayak VG High performance liquid chromatographic determination

of albendazole in pharmaceuticals Indian Drugs 1989 26 494ndash496

17 United States pharmacopeia 23 ed Rockiville United States

Pharmacopeial Convention 1995 37ndash38 1957ndash1963

18 Dicionario de especialidades farmaceuticas 26 ed Rio de Janeiro

Publicac oes Cientıficas 19971998

Received July 31 2000

Accepted February 13 2001

ALBENDAZOLE IN ORAL SUSPENSION 1263

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

Order now

Reprints of this article can also be ordered at

httpwwwdekkercomservletproductDOI101081AL100104151

Request Permission or Order Reprints Instantly

Interested in copying and sharing this article In most cases US Copyright Law requires that you get permission from the articlersquos rightsholder before using copyrighted content

All information and materials found in this article including but not limited to text trademarks patents logos graphics and images (the Materials) are the copyrighted works and other forms of intellectual property of Marcel Dekker Inc or its licensors All rights not expressly granted are reserved

Get permission to lawfully reproduce and distribute the Materials or order reprints quickly and painlessly Simply click on the Request PermissionReprints Here link below and follow the instructions Visit the US Copyright Office for information on Fair Use limitations of US copyright law Please refer to The Association of American Publishersrsquo (AAP) website for guidelines on Fair Use in the Classroom

The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

Page 7: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION

ORDER REPRINTS

The standardization of the chromatographic method for albendazole

determination showed a linear correlation with a 09999 coefficient of cor-

relation between the peak area and the 01 to 150 mgmL albendazole con-

centration (Table 1)

In Table 2 the low variation coefficients (084 175 078)

obtained by the HPLC method for analysis of commercially available

(A and B) and simulated (C) samples confirm the accuracy of this

method The method precision is also confirmed by the results obtained in

the recuperation test It can be checked in Table 3 that there was a slight

variation in percentage of recuperation 9957 to 10083 in relation to

the quantity added

Detection of interferents from the formulation excipients indicated

that they do not influence either method studied

Comparison of accuracy for both methods was made by the F test

where variance of both methods are compared By the results obtained

(Table 4) it was concluded that there is no significant difference at the 5

level between the proposed methods concerning accuracy

For comparison of precision the T test was used With this test it is

possible to assess if the averages of the experimental values of two proposed

methods UV and HLPC show significant difference at the 5 level Table 5

shows the statistical results obtained estimated from a total of 16 degrees of

freedom whose t value calculated of 11463 was lower than t tabulated of

2201 for 95 Thus the two methods do not show significant difference

concerning precision

1260 FREGONEZI-NERY ET AL

Table 2 Statistical Data Obtained in the Determination of the AlbendazoleContent in Commercially Available (A and B) and Simulated (C) Samples by theUV Spectrophotometric Method and High Performance Liquid Chromatography

Method Sample

DeclaredAmount(mg)

FoundAmount(mg)

Coefficientof Variation

()

ConfidenceLimit

Pfrac14 95

A 40000 38155 073 38155plusmn198

UV B 40000 38624 067 38624plusmn185C 40000 42110 062 42110plusmn180

A 40000 38840 084 3884plusmn232HPLC B 40000 37280 175 37280plusmn468

C 40000 42716 078 42710plusmn256

Average of 10 determinations

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

ORDER REPRINTS

CONCLUSION

The methods proposed for determination of albendazole in oral sus-pension showed linear correlation were accurate exact and did not show

ALBENDAZOLE IN ORAL SUSPENSION 1261

Table 4 Experimental Data obtained from Analysis of Variance (ANOVA) WhenComparing Accuracy of Methods UV and HPLC

Resons forVariation

Degree ofLiberty Square Sum Square Mean F PrgtF

Sample 2 162214 81107 57030 00001Treatment 1 063 063 044 05075

Error 56 7964 14Total 59 170241

Table 3 Results of Albendazole Recuperation of Commercially Available (A andB) and Simulated (C) Samples by the UV Spectrophotometric Method and HighPerformance Liquid Chromatography

Method Sample Added (mg) Found (mg) Recovery ()

250 251 10040A 350 352 10057

450 455 10110

250 250 10000UV B 350 349 9971

450 451 10020

250 252 10080C 350 355 10140

450 448 9960

500 498 9960A 600 605 10083

700 703 10043

500 501 10020HPLC B 600 599 9933

700 697 9957

500 500 10000C 600 603 10050

700 701 10014

Average of 2 determinations

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

ORDER REPRINTS

significant statistical difference concerning accuracy nor exactness

Therefore it is possible to use either of the two methods for the analysis

of albendazole in oral suspensions and the choice will depend on method

cost and benefit

REFERENCES

1 Barragry T Anthelmintics a review N Z Vet J 1984 32 161ndash164

2 CookGCUse of benzimidazole chemotherapy in human helminthiases

indications and efficacy Parasitol Today 1990 6(4) 133ndash136

3 Coulaud JP Rossingnol JF Albendazole a new single dose anthel-

mintic Acta Trop 1984 45 87ndash90

4 Gasparine EA Atualizac ao em parasitoses intestinais J Bras Med

1995 68 (4)

5 Bandres JC Clinton White A Jr Samo T Murphy EC Harris

RL Extraparenchymal neurocysticercosis Report of five cases andreview of management Clin Infect Dis 1992 15 799ndash811

6 Alvinerie M Galtier P Simultaneous determination of albendazole

and its principal metabolites in plasma by normal phase high-

performance liquid chromatography J Pharm Biomed Anal 1984

2 73ndash79

7 Bogan JA Marriner S Analysis of benzimidazoles in body fluids by

high-performance liquid chromatography J Pharm Sci 1980 69

422ndash423

8 Hoaksey PE Awadzi K Ward SA Conventry PA Orne MLE

Edwards G Rapid and sensitive method for the determination of alben-

dazole sulphoxide in biological fluids J Chromatogr 1991 566(1)

244ndash249

1262 FREGONEZI-NERY ET AL

Table 5 Results Obtained When Comparing Accuracy ofProposed Methods Using the t Test

Parameters UV HPLC

x 10042 10012

S 061 047n 10 10

Ttabulated for 16 degrees of liberty (Pfrac14 95)frac14 20101

Tcalculated frac14 11463 xxfrac14Mean of experimental values ()S frac14 Standard deviation nfrac14Number of determinations

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

ORDER REPRINTS

9 Hurtado M Medina MT Sotelo J Jung H Sensitive high

performance liquid chromatographic assay for albendazole and its

main metabolite albendazole sulphoxid in plasma and cerebrospinal

fluid J Chromatogr 1989 494 403ndash407

10 Meulemans A Giovangeli MD Mohler J Vulpillat M Hay

JM Saimot AG High performance liquid chromatography of

albendazol and its sulfoxide metabolite in human organs and fluids

during hydatidosis J Liq Chromatog 1984 7 569ndash580

11 Zeugin T Sysset T Cotting J Therapeutic monitoring of albenda-

zole a high performance liquid chromatography method for determi-

nation of its active metabolite albendazole sulfoxid Ther Drug Monit

1990 12 187ndash190

12 Bergold AM Korolkovas A Doseamento do albendazol como

materia prima e em comprimidos em meio nao aquoso com acido

perclorico Rev Farm Bioquim S Paulo 1993 29(1) 31ndash34

13 Laurentis N Milillo MA Bruno S Determination of albendazole

as raw material and in tablets by nonaqueous tituration with sodium

methylate solution Rev Farm Bioquim S Paulo 1997 33(1) 23ndash27

14 Long AR Hsieh LC Short CR Barker SA Isocratic liquid

chromatographywith photodiode array characterization JChromatogr

1989 475 404ndash411

15 Mandal SC Bhattacharyya M Maity AK Gupta BK Ghosal

SKL Determination of albendazole in tablet formulations by UV

spectrophotometric method Indian Drugs 1992 29(7) 323ndash324

16 Sane RT Samant RS Joshi MD Purandare SM Tembe PB

Nayak VG High performance liquid chromatographic determination

of albendazole in pharmaceuticals Indian Drugs 1989 26 494ndash496

17 United States pharmacopeia 23 ed Rockiville United States

Pharmacopeial Convention 1995 37ndash38 1957ndash1963

18 Dicionario de especialidades farmaceuticas 26 ed Rio de Janeiro

Publicac oes Cientıficas 19971998

Received July 31 2000

Accepted February 13 2001

ALBENDAZOLE IN ORAL SUSPENSION 1263

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

Order now

Reprints of this article can also be ordered at

httpwwwdekkercomservletproductDOI101081AL100104151

Request Permission or Order Reprints Instantly

Interested in copying and sharing this article In most cases US Copyright Law requires that you get permission from the articlersquos rightsholder before using copyrighted content

All information and materials found in this article including but not limited to text trademarks patents logos graphics and images (the Materials) are the copyrighted works and other forms of intellectual property of Marcel Dekker Inc or its licensors All rights not expressly granted are reserved

Get permission to lawfully reproduce and distribute the Materials or order reprints quickly and painlessly Simply click on the Request PermissionReprints Here link below and follow the instructions Visit the US Copyright Office for information on Fair Use limitations of US copyright law Please refer to The Association of American Publishersrsquo (AAP) website for guidelines on Fair Use in the Classroom

The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

Page 8: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION

ORDER REPRINTS

CONCLUSION

The methods proposed for determination of albendazole in oral sus-pension showed linear correlation were accurate exact and did not show

ALBENDAZOLE IN ORAL SUSPENSION 1261

Table 4 Experimental Data obtained from Analysis of Variance (ANOVA) WhenComparing Accuracy of Methods UV and HPLC

Resons forVariation

Degree ofLiberty Square Sum Square Mean F PrgtF

Sample 2 162214 81107 57030 00001Treatment 1 063 063 044 05075

Error 56 7964 14Total 59 170241

Table 3 Results of Albendazole Recuperation of Commercially Available (A andB) and Simulated (C) Samples by the UV Spectrophotometric Method and HighPerformance Liquid Chromatography

Method Sample Added (mg) Found (mg) Recovery ()

250 251 10040A 350 352 10057

450 455 10110

250 250 10000UV B 350 349 9971

450 451 10020

250 252 10080C 350 355 10140

450 448 9960

500 498 9960A 600 605 10083

700 703 10043

500 501 10020HPLC B 600 599 9933

700 697 9957

500 500 10000C 600 603 10050

700 701 10014

Average of 2 determinations

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

ORDER REPRINTS

significant statistical difference concerning accuracy nor exactness

Therefore it is possible to use either of the two methods for the analysis

of albendazole in oral suspensions and the choice will depend on method

cost and benefit

REFERENCES

1 Barragry T Anthelmintics a review N Z Vet J 1984 32 161ndash164

2 CookGCUse of benzimidazole chemotherapy in human helminthiases

indications and efficacy Parasitol Today 1990 6(4) 133ndash136

3 Coulaud JP Rossingnol JF Albendazole a new single dose anthel-

mintic Acta Trop 1984 45 87ndash90

4 Gasparine EA Atualizac ao em parasitoses intestinais J Bras Med

1995 68 (4)

5 Bandres JC Clinton White A Jr Samo T Murphy EC Harris

RL Extraparenchymal neurocysticercosis Report of five cases andreview of management Clin Infect Dis 1992 15 799ndash811

6 Alvinerie M Galtier P Simultaneous determination of albendazole

and its principal metabolites in plasma by normal phase high-

performance liquid chromatography J Pharm Biomed Anal 1984

2 73ndash79

7 Bogan JA Marriner S Analysis of benzimidazoles in body fluids by

high-performance liquid chromatography J Pharm Sci 1980 69

422ndash423

8 Hoaksey PE Awadzi K Ward SA Conventry PA Orne MLE

Edwards G Rapid and sensitive method for the determination of alben-

dazole sulphoxide in biological fluids J Chromatogr 1991 566(1)

244ndash249

1262 FREGONEZI-NERY ET AL

Table 5 Results Obtained When Comparing Accuracy ofProposed Methods Using the t Test

Parameters UV HPLC

x 10042 10012

S 061 047n 10 10

Ttabulated for 16 degrees of liberty (Pfrac14 95)frac14 20101

Tcalculated frac14 11463 xxfrac14Mean of experimental values ()S frac14 Standard deviation nfrac14Number of determinations

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

ORDER REPRINTS

9 Hurtado M Medina MT Sotelo J Jung H Sensitive high

performance liquid chromatographic assay for albendazole and its

main metabolite albendazole sulphoxid in plasma and cerebrospinal

fluid J Chromatogr 1989 494 403ndash407

10 Meulemans A Giovangeli MD Mohler J Vulpillat M Hay

JM Saimot AG High performance liquid chromatography of

albendazol and its sulfoxide metabolite in human organs and fluids

during hydatidosis J Liq Chromatog 1984 7 569ndash580

11 Zeugin T Sysset T Cotting J Therapeutic monitoring of albenda-

zole a high performance liquid chromatography method for determi-

nation of its active metabolite albendazole sulfoxid Ther Drug Monit

1990 12 187ndash190

12 Bergold AM Korolkovas A Doseamento do albendazol como

materia prima e em comprimidos em meio nao aquoso com acido

perclorico Rev Farm Bioquim S Paulo 1993 29(1) 31ndash34

13 Laurentis N Milillo MA Bruno S Determination of albendazole

as raw material and in tablets by nonaqueous tituration with sodium

methylate solution Rev Farm Bioquim S Paulo 1997 33(1) 23ndash27

14 Long AR Hsieh LC Short CR Barker SA Isocratic liquid

chromatographywith photodiode array characterization JChromatogr

1989 475 404ndash411

15 Mandal SC Bhattacharyya M Maity AK Gupta BK Ghosal

SKL Determination of albendazole in tablet formulations by UV

spectrophotometric method Indian Drugs 1992 29(7) 323ndash324

16 Sane RT Samant RS Joshi MD Purandare SM Tembe PB

Nayak VG High performance liquid chromatographic determination

of albendazole in pharmaceuticals Indian Drugs 1989 26 494ndash496

17 United States pharmacopeia 23 ed Rockiville United States

Pharmacopeial Convention 1995 37ndash38 1957ndash1963

18 Dicionario de especialidades farmaceuticas 26 ed Rio de Janeiro

Publicac oes Cientıficas 19971998

Received July 31 2000

Accepted February 13 2001

ALBENDAZOLE IN ORAL SUSPENSION 1263

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

Order now

Reprints of this article can also be ordered at

httpwwwdekkercomservletproductDOI101081AL100104151

Request Permission or Order Reprints Instantly

Interested in copying and sharing this article In most cases US Copyright Law requires that you get permission from the articlersquos rightsholder before using copyrighted content

All information and materials found in this article including but not limited to text trademarks patents logos graphics and images (the Materials) are the copyrighted works and other forms of intellectual property of Marcel Dekker Inc or its licensors All rights not expressly granted are reserved

Get permission to lawfully reproduce and distribute the Materials or order reprints quickly and painlessly Simply click on the Request PermissionReprints Here link below and follow the instructions Visit the US Copyright Office for information on Fair Use limitations of US copyright law Please refer to The Association of American Publishersrsquo (AAP) website for guidelines on Fair Use in the Classroom

The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

Page 9: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION

ORDER REPRINTS

significant statistical difference concerning accuracy nor exactness

Therefore it is possible to use either of the two methods for the analysis

of albendazole in oral suspensions and the choice will depend on method

cost and benefit

REFERENCES

1 Barragry T Anthelmintics a review N Z Vet J 1984 32 161ndash164

2 CookGCUse of benzimidazole chemotherapy in human helminthiases

indications and efficacy Parasitol Today 1990 6(4) 133ndash136

3 Coulaud JP Rossingnol JF Albendazole a new single dose anthel-

mintic Acta Trop 1984 45 87ndash90

4 Gasparine EA Atualizac ao em parasitoses intestinais J Bras Med

1995 68 (4)

5 Bandres JC Clinton White A Jr Samo T Murphy EC Harris

RL Extraparenchymal neurocysticercosis Report of five cases andreview of management Clin Infect Dis 1992 15 799ndash811

6 Alvinerie M Galtier P Simultaneous determination of albendazole

and its principal metabolites in plasma by normal phase high-

performance liquid chromatography J Pharm Biomed Anal 1984

2 73ndash79

7 Bogan JA Marriner S Analysis of benzimidazoles in body fluids by

high-performance liquid chromatography J Pharm Sci 1980 69

422ndash423

8 Hoaksey PE Awadzi K Ward SA Conventry PA Orne MLE

Edwards G Rapid and sensitive method for the determination of alben-

dazole sulphoxide in biological fluids J Chromatogr 1991 566(1)

244ndash249

1262 FREGONEZI-NERY ET AL

Table 5 Results Obtained When Comparing Accuracy ofProposed Methods Using the t Test

Parameters UV HPLC

x 10042 10012

S 061 047n 10 10

Ttabulated for 16 degrees of liberty (Pfrac14 95)frac14 20101

Tcalculated frac14 11463 xxfrac14Mean of experimental values ()S frac14 Standard deviation nfrac14Number of determinations

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

ORDER REPRINTS

9 Hurtado M Medina MT Sotelo J Jung H Sensitive high

performance liquid chromatographic assay for albendazole and its

main metabolite albendazole sulphoxid in plasma and cerebrospinal

fluid J Chromatogr 1989 494 403ndash407

10 Meulemans A Giovangeli MD Mohler J Vulpillat M Hay

JM Saimot AG High performance liquid chromatography of

albendazol and its sulfoxide metabolite in human organs and fluids

during hydatidosis J Liq Chromatog 1984 7 569ndash580

11 Zeugin T Sysset T Cotting J Therapeutic monitoring of albenda-

zole a high performance liquid chromatography method for determi-

nation of its active metabolite albendazole sulfoxid Ther Drug Monit

1990 12 187ndash190

12 Bergold AM Korolkovas A Doseamento do albendazol como

materia prima e em comprimidos em meio nao aquoso com acido

perclorico Rev Farm Bioquim S Paulo 1993 29(1) 31ndash34

13 Laurentis N Milillo MA Bruno S Determination of albendazole

as raw material and in tablets by nonaqueous tituration with sodium

methylate solution Rev Farm Bioquim S Paulo 1997 33(1) 23ndash27

14 Long AR Hsieh LC Short CR Barker SA Isocratic liquid

chromatographywith photodiode array characterization JChromatogr

1989 475 404ndash411

15 Mandal SC Bhattacharyya M Maity AK Gupta BK Ghosal

SKL Determination of albendazole in tablet formulations by UV

spectrophotometric method Indian Drugs 1992 29(7) 323ndash324

16 Sane RT Samant RS Joshi MD Purandare SM Tembe PB

Nayak VG High performance liquid chromatographic determination

of albendazole in pharmaceuticals Indian Drugs 1989 26 494ndash496

17 United States pharmacopeia 23 ed Rockiville United States

Pharmacopeial Convention 1995 37ndash38 1957ndash1963

18 Dicionario de especialidades farmaceuticas 26 ed Rio de Janeiro

Publicac oes Cientıficas 19971998

Received July 31 2000

Accepted February 13 2001

ALBENDAZOLE IN ORAL SUSPENSION 1263

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Order now

Reprints of this article can also be ordered at

httpwwwdekkercomservletproductDOI101081AL100104151

Request Permission or Order Reprints Instantly

Interested in copying and sharing this article In most cases US Copyright Law requires that you get permission from the articlersquos rightsholder before using copyrighted content

All information and materials found in this article including but not limited to text trademarks patents logos graphics and images (the Materials) are the copyrighted works and other forms of intellectual property of Marcel Dekker Inc or its licensors All rights not expressly granted are reserved

Get permission to lawfully reproduce and distribute the Materials or order reprints quickly and painlessly Simply click on the Request PermissionReprints Here link below and follow the instructions Visit the US Copyright Office for information on Fair Use limitations of US copyright law Please refer to The Association of American Publishersrsquo (AAP) website for guidelines on Fair Use in the Classroom

The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

Dow

nloa

ded

by [

The

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anch

este

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Dec

embe

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14

Page 10: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION

ORDER REPRINTS

9 Hurtado M Medina MT Sotelo J Jung H Sensitive high

performance liquid chromatographic assay for albendazole and its

main metabolite albendazole sulphoxid in plasma and cerebrospinal

fluid J Chromatogr 1989 494 403ndash407

10 Meulemans A Giovangeli MD Mohler J Vulpillat M Hay

JM Saimot AG High performance liquid chromatography of

albendazol and its sulfoxide metabolite in human organs and fluids

during hydatidosis J Liq Chromatog 1984 7 569ndash580

11 Zeugin T Sysset T Cotting J Therapeutic monitoring of albenda-

zole a high performance liquid chromatography method for determi-

nation of its active metabolite albendazole sulfoxid Ther Drug Monit

1990 12 187ndash190

12 Bergold AM Korolkovas A Doseamento do albendazol como

materia prima e em comprimidos em meio nao aquoso com acido

perclorico Rev Farm Bioquim S Paulo 1993 29(1) 31ndash34

13 Laurentis N Milillo MA Bruno S Determination of albendazole

as raw material and in tablets by nonaqueous tituration with sodium

methylate solution Rev Farm Bioquim S Paulo 1997 33(1) 23ndash27

14 Long AR Hsieh LC Short CR Barker SA Isocratic liquid

chromatographywith photodiode array characterization JChromatogr

1989 475 404ndash411

15 Mandal SC Bhattacharyya M Maity AK Gupta BK Ghosal

SKL Determination of albendazole in tablet formulations by UV

spectrophotometric method Indian Drugs 1992 29(7) 323ndash324

16 Sane RT Samant RS Joshi MD Purandare SM Tembe PB

Nayak VG High performance liquid chromatographic determination

of albendazole in pharmaceuticals Indian Drugs 1989 26 494ndash496

17 United States pharmacopeia 23 ed Rockiville United States

Pharmacopeial Convention 1995 37ndash38 1957ndash1963

18 Dicionario de especialidades farmaceuticas 26 ed Rio de Janeiro

Publicac oes Cientıficas 19971998

Received July 31 2000

Accepted February 13 2001

ALBENDAZOLE IN ORAL SUSPENSION 1263

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

Order now

Reprints of this article can also be ordered at

httpwwwdekkercomservletproductDOI101081AL100104151

Request Permission or Order Reprints Instantly

Interested in copying and sharing this article In most cases US Copyright Law requires that you get permission from the articlersquos rightsholder before using copyrighted content

All information and materials found in this article including but not limited to text trademarks patents logos graphics and images (the Materials) are the copyrighted works and other forms of intellectual property of Marcel Dekker Inc or its licensors All rights not expressly granted are reserved

Get permission to lawfully reproduce and distribute the Materials or order reprints quickly and painlessly Simply click on the Request PermissionReprints Here link below and follow the instructions Visit the US Copyright Office for information on Fair Use limitations of US copyright law Please refer to The Association of American Publishersrsquo (AAP) website for guidelines on Fair Use in the Classroom

The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14

Page 11: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION

Order now

Reprints of this article can also be ordered at

httpwwwdekkercomservletproductDOI101081AL100104151

Request Permission or Order Reprints Instantly

Interested in copying and sharing this article In most cases US Copyright Law requires that you get permission from the articlersquos rightsholder before using copyrighted content

All information and materials found in this article including but not limited to text trademarks patents logos graphics and images (the Materials) are the copyrighted works and other forms of intellectual property of Marcel Dekker Inc or its licensors All rights not expressly granted are reserved

Get permission to lawfully reproduce and distribute the Materials or order reprints quickly and painlessly Simply click on the Request PermissionReprints Here link below and follow the instructions Visit the US Copyright Office for information on Fair Use limitations of US copyright law Please refer to The Association of American Publishersrsquo (AAP) website for guidelines on Fair Use in the Classroom

The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

Dow

nloa

ded

by [

The

Uni

vers

ity o

f M

anch

este

r L

ibra

ry]

at 2

003

19

Dec

embe

r 20

14