Factors Affecting Stability of Quinidine - PowerPoint PPT Presentation

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Factors Affecting Stability of Quinidine

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Quinidine is a prescription drug used to treat abnormal heart rhythms. ... Like all drugs, Quinidine is packaged with specific storage instructions ... – PowerPoint PPT presentation

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Title: 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
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