Factors Affecting Stability of Quinidine

1
Factors Affecting Stability of Quinidine

• Melissa Usry and Sharmistha Basu-Dutt
• Department of Chemistry, University of West
  Georgia, Carrollton, GA 30118

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 ?max.

• Introduction
• Quinidine 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.

Results

• Procedure
• Step 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 ?max
• Record absorbance at ?max 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

Structure of Quinidine
Calibration Curve
UV-Vis Spectra Scan to obtain ?max
UV-Vis Spectra of pH stressed Quinidine
Effect of pH on Quinidine Stability
Effect of Temperature on Quinidine Stability
Effect of alcohol on Quinidine Stability
Summary of Results
Regression Equation y Ax3 Bx2 Cx D Regression Equation y Ax3 Bx2 Cx D Regression Equation y Ax3 Bx2 Cx D Regression Equation y Ax3 Bx2 Cx D Regression Equation y Ax3 Bx2 Cx D
Type 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. Alcohol Addition 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

• Discussion of Results
• UV-Vis spectra show that ?max 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 ?max, therefore indicating formation of a
  new product that will be analyzed using a GC-MS
  in a future project

Acknowledgements NSF-STEP GEMS Grant DUE-0336571