Factors Affecting Stability of Quinidine
Melissa Usry
July 28, 2006
Department of Chemistry
Under the supervision of Sharmistha Basu-Dutt
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.
The purpose of this study was to determine the effects of stressed conditions on
the Quinidine medication. Over the course of the experiment, the stability of
Quinidine is reported under stressed conditions of pH, temperature and presence
of alcohol.
The procedures include placing a sample solution of quinidine under
various stressed conditions, and analyze the results due to these alterations.
The first step in this process was to prepare the stock solution, which consisted
of ten milligrams of pure quinidine added to ten milliliters. In order to complete
the stock solution, the dilution must be ten folded by adding nine milliliters of
water to one milliliter of the pure quinidine solution. Using this stock solution, the
diluted solutions are prepared by taking 0.2 milliliters, 0.5 milliliters, 1 milliliter,
and 2 milliliters, and placing them in four individual test tubes. Lastly, water is
added to each to formulate a final volume of five milliliters. These diluted
solutions were used to generate the calibration curve based on the data reported
by the UV/Vis Spectrophotometer. Samples of each solution, beginning with the
ten fold stock solution, were placed in a cuvette, which was then inserted into the
UV/Vis Spectrophotometer. A scan of wavelengths ranging from 280 to 340
nanometers was tested, and the wavelength at which the maximum absorbance
occurred was designated λmax. The absorbance resulting from each solution is
plotted on a graph, and a best fit line was drawn between the various points. The
equation of this line was used to calculate the concentrations of the samples
based on their absorbance ratios. After obtaining the calibration curve, the
samples were placed under assorted stressed conditions. The first stressed
condition tested was the increase of temperature. A sample of the stock solution
was heated, and examined at various temperatures using the UV/Vis. The
absorbance rates, and therefore the concentrations, at each elevated
temperatures were recorded. The second stressed condition tested was the
change of pH in the solution. This experiment began by first finding the pH of the
original stock solution using a pH probe. Next, drops of base were added to the
solution with the pH being tested after each addition, and the degraded sample
tested using the UV/Vis. The same steps were followed with an acid, and the
resulting concentrations recorded. The last stressed condition placed on the
quinidine solution was the addition of alcohol. As drops of alcohol were added,
the sample was tested in the UV/Vis, and the change in concentrations recorded.
After placing the solution under these different stressed conditions, the change in
concentrations of each experiment were plotted individually on a graph using
Excel. A polynomial curve fitting was used to obtain polynomial coefficients to
study the impact of these various factors on the stability of Quinidine. These
coefficients were analyzed, and were the basis of the results formulated.
The UV/Vis Spectrophotometer was an important machine used over the
course of these research experiments. The particular Spectrophotometer used in
these trials was a Jasco V-570. 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. The machine is connected to a computer, where the results of the scan
are presented and analyzed.
The information presented through the UV/Vis suggested the wavelength
at which the maximum absorbance occurred was 331 nanometers. Therefore,
the change in absorbance for each experiment was recorded at this point. The
graphs formulated using Excel were finally analyzed. Each of the graphs
revealed a loss of stability leading to a concentration decrease according to a 3rd
order polynomial. Also, the coefficients of the regression equations formed by
each trend line were studied, and revealed that the stressed conditions of pH
affected the stability of Quinidine the most. Furthermore, the change of pH in the
solution caused a shift in the λmax, therefore indicating the formation of a new
product. This was the extent of results reached based on the research
completed at the conclusion of the summer semester program.
The discovery of the shift due to pH led to the plans for future projects
using a GC-MS. Also, the trials will be tested a second time to verify results
formulated during these experiments. Furthermore, plans to continue further
research into this study are in effect and will be reported following the Fall
semester.