Measurements of Thermodynamic Acid Dissociation Constants for Three HMG-CoA Reductase Inhibitors by using RPLC and Study of Validation in Pharmaceutical Tablets

Abstract

Background: Present work was designed about the assignation of thermodynamic acid dissociation constants (pKa) of pravastatin, atorvastatin and rosuvastatin by using RPLC method. In the experiment, methanol-water binary mixture was chosen as hydroorganic solvent mixture. Method: Chromatographic study was performed with Nucleosil 300-5C4 column (5µm, 250x4.6 mm, I.D.) and the flow rate of the experiment was adjusted at 1 mL/min. The thermodynamic acid dissociation constant values and the intrinsic retention factors were estimated by use of a non-linear least squares fit of the data. The realibility of the RPLC methodology was investigated statistically using the difference between the experimental and theoretical results. Aqueous pKa values were also estimated with extrapolation by means of the Yasuda-Shedlovsky and mole fraction equations. Conclusion: Availability of present procedure in order to quantitatively determine the studied compounds was verified by the validation in suitability with the requirements laid down via ICH (International Conference on Harmonization) guidelines. Results of the analysis show that the method can be used for the estimation of studied drugs in pharmaceutical formulations, with great recovery, well precision and accuracy. Keywords: Statins, chromatographic retention, polarity parameter, thermodynamic dissociation constant, RPLC, method validation.