determination of albendazole in oral suspension
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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
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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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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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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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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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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
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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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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
by [
The
Uni
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ity o
f M
anch
este
r L
ibra
ry]
at 2
003
19
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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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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
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![Page 4: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION](https://reader035.vdocuments.us/reader035/viewer/2022081123/5750abc51a28abcf0ce1f627/html5/thumbnails/4.jpg)
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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ry]
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embe
r 20
14
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
Dow
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ded
by [
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Uni
vers
ity o
f M
anch
este
r L
ibra
ry]
at 2
003
19
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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este
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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
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embe
r 20
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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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embe
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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
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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nloa
ded
by [
The
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vers
ity o
f M
anch
este
r L
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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
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ded
by [
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ity o
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embe
r 20
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![Page 5: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION](https://reader035.vdocuments.us/reader035/viewer/2022081123/5750abc51a28abcf0ce1f627/html5/thumbnails/5.jpg)
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
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
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
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
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 6: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION](https://reader035.vdocuments.us/reader035/viewer/2022081123/5750abc51a28abcf0ce1f627/html5/thumbnails/6.jpg)
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
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
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](https://reader035.vdocuments.us/reader035/viewer/2022081123/5750abc51a28abcf0ce1f627/html5/thumbnails/7.jpg)
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](https://reader035.vdocuments.us/reader035/viewer/2022081123/5750abc51a28abcf0ce1f627/html5/thumbnails/8.jpg)
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](https://reader035.vdocuments.us/reader035/viewer/2022081123/5750abc51a28abcf0ce1f627/html5/thumbnails/9.jpg)
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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Reprints of this article can also be ordered at
httpwwwdekkercomservletproductDOI101081AL100104151
Request Permission or Order Reprints Instantly
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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
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![Page 10: DETERMINATION OF ALBENDAZOLE IN ORAL SUSPENSION](https://reader035.vdocuments.us/reader035/viewer/2022081123/5750abc51a28abcf0ce1f627/html5/thumbnails/10.jpg)
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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
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](https://reader035.vdocuments.us/reader035/viewer/2022081123/5750abc51a28abcf0ce1f627/html5/thumbnails/11.jpg)
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