Factors Affecting Stability of QuinidineMelissa Usry and Sharmistha Basu-Dutt

Department of Chemistry, University of West Georgia, Carrollton, GA 30118

IntroductionQuinidine is a prescription drug used to treat abnormal heart rhythms. The medication regulates the flow of sodium into heart cells helping to return the heart to a regular pace and assisting in maintaining normal heartbeat. Like all drugs, Quinidine is packaged with specific storage instructions containing the proper method for handling the product. The pharmacist as well as the patient must be aware of risks associated with improper handling or storage of the drug.•In this study, the stability of Quinidine is reported under stressed conditions of pH, temperature and presence of alcohol.

Discussion of Results•UV-Vis spectra show that λmax for Quinidine appears at 331 nm

•Subjecting Quinidine to stressed conditions of pH, temperature and alcohol resulted in loss of stability leading to a concentration decrease according to a 3rd order polynomial

•Stressed conditions of pH affected the stability of Quinidine the most and resulted in a shift in its λmax, therefore indicating formation of a new product that will be analyzed using a GC-MS in a future project

ProcedureStep 1 – Prepare stock solution.

•10 mg of quinidine gluconate + 10 mL of water•10-fold dilution using 1 mL of soln. + 9 mL of water

Step 2 – Prepare diluted solutions to create calibration curve.

•Transfer 0.2 mL, 0.5 mL, 1 mL, and 2 mL into four test tubes and add water to obtain a final volume of 5 mL

Step 3 – Obtain UV/Vis spectra of samples.•Conduct a scan of the stock Quinidine solution between 280 – 340 nm using a Jasco V-570 UV/Vis/NIR Spectrophotometer•Identify the wavelength at which maximum absorbance takes place and designate as λmax

•Record absorbance at λmax for all samples to create calibration curve•Study the impact of various types of stressed conditions

Step 4 – Subject Quinidine solutions to stress.•Stress and degrade the samples by subjecting them to a range of temperatures, pH and alcohol levels•Obtain absorbance changes as a function of temperature, pH and volume of alcohol added

Step 5 – Curve Fitting using Microsoft Excel.• A best fit linear regression equation provides the relationship between absorbance and concentration from the calibration curve•A polynomial curve fitting is used to obtain polynomial coefficients to study the impact of various factors on the stability of Quinidine

Results

Acknowledgements

NSF-STEP GEMS Grant #DUE-0336571

0.4

1

0.6

0.8

280 340300 320

Abs

Wavelength [nm]

331 nm, 0.9867

0.1

0.8

0.2

0.4

0.6

280 340300 320

Abs

Wavelength [nm]

331 nm, 0.62428

Effect of Temperature on ConcentrationDiluted Stock Solution

y = -2E-05x3 + 0.0019x2 - 0.064x + 0.7174

R2 = 0.9162

0

0.02

0.04

0.06

0.08

0.1

0.12

0.14

0.16

0.18

10 20 30 40 50

Temperature

Co

ncen

trati

on

Effect of Temperature on ConcentrationStock Solution

y = 3E- 08x3 - 4E- 06x2 + 0.0001x + 0.117

R2 = 0.9912

0.1166

0.1168

0.117

0.1172

0.1174

0.1176

0.1178

0.118

0.1182

0.1184

20 30 40 50 60

Temperature

Co

ncen

trati

on

Effect of pH on Concentrationaddition of 0.1M NaOH

y = 0.0494x3 - 1.7026x2 + 19.5x - 74.152

R2 = 0.9568

0.030.040.050.060.070.080.090.1

10.5 11 11.5 12 12.5

pH

Co

nce

ntr

atio

n

Effect of pH on Concentrationaddition of 0.1M HCl

y = -0.0013x3 + 0.0039x2 + 0.0357x - 0.0079R2 = 0.9826

0.06

0.08

0.1

0.12

2 2.2 2.4 2.6 2.8 3 3.2 3.4 3.6 3.8 4

pH

Effect of Alcohol on Concentrationaddition of MeOH

y = -5E-06x3 + 0.0003x2 - 0.0074x + 0.111

R2 = 0.9842

0.04

0.05

0.06

0.07

0.08

0.09

0.1

0.11

0.12

0 5 10 15 20 25 30 35

Drops of MeOH

Co

nc

en

tra

tio

n

Regression Equation y = Ax3 + Bx2 + Cx + DType of Plot A B C D

Concentration v. Temperature

Stock Solution

3E-8 -4E-6 0.0001 0.117

Concentration v. Temperature

Diluted Stock Solution

-2E-5 0.0019 -0.064 0.7174

Concentration v. AlcoholAddition of MeOH

-5E-6 0.0003 -0.0074 0.111

Concentration v. pH Addition of

NaOH

0.0494 -1.7026 19.5 -74.152

Concentration v. pH Addition of HCl

-0.0013 0.0039 0.0357 -0.0079

Principle of Operation of UV-Vis Spectrophotometery

The UV/Vis Spectrophotometer is a machine used to test the absorbance ratios of certain compounds using ultraviolet and visible light beams. A sample beam is passed through a small transparent container (cuvette) containing a solution of the compound being studied in a transparent solvent. A reference beam is passed through an identical cuvette containing only the solvent. The intensities of these light beams are then measured by electronic detectors and compared. Absorbance is displayed on the vertical axis, while the UV and/or visible region scanned is shown on the horizontal axis. The UV region tested is generally from 200 to 400 nm. The wavelength of maximum absorbance is a characteristic value, designated as λmax.

Structure of Quinidine

UV-Vis Spectra Scan to obtain λmax

Calibration Curve

Effect of pH on Quinidine Stability

UV-Vis Spectra of pH stressed Quinidine

Effect of Temperature on Quinidine Stability Effect of alcohol on Quinidine Stability

Summary of Results

Calibration Curve

y = 8.2972x - 0.0069

R2 = 0.9999

0

0.2

0.4

0.6

0.8

1

1.2

0 0.05 0.1 0.15

Concentration (mg/mL)

Ab

so

rban

ce