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Factors Affecting Stability of Quinidine Melissa Usry and Sharmistha Basu-Dutt Department of Chemistry, University of West Georgia, Carrollton, GA 30118 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. Discussion of Results UV-Vis spectra show that λ 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 3 rd order polynomial Stressed conditions of pH affected the stability of Quinidine the most and resulted in a shift in its λ max, therefore indicating formation of a new product that will be analyzed using a GC-MS in a future project 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 λ max Record absorbance at λ 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 Results Acknowledgements NSF-STEP GEMS Grant #DUE-0336571 Regression Equation y = Ax 3 + Bx 2 + Cx + D Type of PlotABCD Concentration v. Temperature Stock Solution 3E-8-4E-60.00010.117 Concentration v. Temperature Diluted Stock Solution -2E-50.0019-0.0640.7174 Concentration v. Alcohol Addition of MeOH -5E-60.0003-0.00740.111 Concentration v. pH Addition of NaOH 0.0494-1.702619.5-74.152 Concentration v. pH Addition of HCl - 0.0013 0.00390.0357-0.0079 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 λ max. Structure of Quinidine UV-Vis Spectra Scan to obtain λ max Calibration Curve Effect of pH on Quinidine Stability UV-Vis Spectra of pH stressed Quinidine Effect of Temperature on Quinidine StabilityEffect of alcohol on Quinidine Stability Summary of Results
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