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Determination of pravastatin and separation of its interconversion products in acidic media using capillary electrophoresis

Pravastatin belongs to a class of lipid-lowering drugs called statins. These compounds reduce levels of circulating atherogenic lipoproteins by competitive inhibition of the microsomal enzyme 3-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, a critical intermediary in the cholesterol pathway. Statins are currently the most therapeutically effective drugs available for reducing LDL cholesterol and triglyceride levels in the blood stream of patients at risk of cardiovascular disease (1). In the work we report the development of a capillary zone electrophoresis method for determination of pravastatin. The strong electric field (30 kV) and alkaline running buffer (pH 9.3) generate strong electroosmotic flow allowing the determination of the drug within 2.5 min. The assay procedure listed in Ph. Eur. used the HPLC with UV detection (retention time about 21 min). Application of the CZE to the pravastatin determination in a pharmaceutical dosage form, resulted in acceptable deviation from the stated concentration. Therefore, the developed CZE method can be used as a versatile alternative over the liquid chromatographic method for the analysis of pravastatin in bulk form and pharmaceuticals. Pravastatin is a  -hydroxyacid, which exists in solution with its lactone equilibrium product in a pH-dependent manner. At acidic pH, the hydroxy acid form of pravastatin can reversibly lactonize. Additionally, pravastatin is also susceptible to an isomerization reaction at acidic pH, which is relatively rapid (2). In the present work a micellar electrokinetic chromatographic approach was chosen to develop a method able to separate the drug and its interconversion products. Proposed method allows baseline separation of pravastatin and all its impurities in acidic media. The developed MEKC method has shorter runtime when compared with the reported LC method for separation of pravastatin related impurities.

pravastatin; capillary zone electrophoresis; micellar electrokinetic chromatography; determination; related impurities

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