A Review of Current Trends and Advances in Analytical Methods for Determination of Statins: Chromatography and Capillary Electrophoresis

Abstract

Statins are the most effective drugs currently available for treating hypercholesterolemia, as they reduce the level of total and low-density lipoprotein cholesterol, triglycerides and apolipoprotein B in plasma of patients at risk of cardiovascular disease, even they are currently among the most widely prescribed drugs. They are specific and competitive inhibitors of 3-hydroxy-3-methlyglutaryl coenzyme A (HMG-CoA) reductase, which is a key enzyme that catalyzes the conversion of HMG-CoA to mevalonate. This is an early rate-limiting step in the cholesterol biosynthetic pathway. Statins include natural (lovastatin), semi-synthetic (simvastatin, and pravastatin) and synthetic compounds (fluvastatin, atorvastatin, rosuvastatin and pitavastatin). All statins share an HMG-like pharmacophore, which may be present in the active hydroxy acid form or in the inactive lactone form. Lovastatin and simvastatin are administered as lactone prodrugs and subsequently hydrolyzed to active metabolites, while other statins are formulated in β-hydroxy acid form. The interconversion between lactone and hydroxy acid forms of statin molecules is a highly pH dependent. Statin use has soared over the last decade, and is expected to increase further in the years ahead because high cholesterol and cardiovascular diseases are being diagnosed more frequently. For this reason, rapid and effective ways for the identification and determination of these drugs are highly required. The therapy with statins is considered for the long-term use and the purity evaluation of these drugs is of great significance. Bioanalytical methods are necessary for the clinical trials, for therapeutic drug monitoring and individual dosage scheme adjustment of statins. High performance liquid chromatography with various types of detection is the technique of choice in developing new methods for analysis of statin molecules. This chapter presents recent trends and advances in chromatographic and capillary electrophoretic methods for the determination of statin drugs in various fields of application.