Development of chromatographic method for determination of drugs reducing cholesterol level.

Hyperlipidemia (HLP) is a group of lipid metabolism disorders with various pathogenesis. Its characteristic feature is an increase in cholesterol level, especially the low density lipoprotein fraction (LDL) level or triglyceride level in blood. An increase in total and LDL cholesterol level is related to the increased risk of ischemic heart disease as well as cerebral, coronary and peripheral circulation disorders. The medications against hyperlipidemia and cholesterol level reduction are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (HMGCoA) also known as statins and aryloxyalkylcarboxylic acid derivatives, also known as fibrates. Statins inhibit biosynthesis of endogenous cholesterol at the mevalonic acid synthesis level and reduce of total cholesterol, LDL fraction and triglycerides levels in plasma and increases HDL fraction level. A mother compound for a group of 3hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (HMG-CoA) is lovastatin. Currently, a semi-synthetic derivatives are available (simvastatin and pravastatin sodium), as well as synthetic compounds ñ atorvastatin calcium, fluvastatin sodium and lately rosuvastatin calcium (1ñ4). The fibrates inhibit VLDL lipoprotein synthesis in liver and accelerate catabolism by increasing lipoprotein lipase activity. Also they improve HDL level and affect the return of cholesterol. A clofibrate is a mother compound of the derivatives of aryloxyalkylcarboxylic acids. This class of drugs include new generation drugs: bezafibrate, ciprofibrate, etofibrate, fenofibrate and gemfibrozil (1ñ4). The available literature of the last several years includes several publications describing separately an identification and determination of lovastatin derivatives and derivates of aryloxyalkylcarboxylic acids in pharmaceutical products and biological material. HPLC or UPLC methods with octadecyl packed column with UV-VIS detector (11, 13ñ16) and mass detector (12), the capillary electrophoresis (9) and electrochemical methods ( 7) are used for statins analysis. The tests on fibrates relied mainly on the HPLC method with Symmetry ODS or Hypersil ODS columns using a spectrophotometric detector (12) or mass spectrometry (10, 12), the method of capillary electrophoresis (6) and gas chromatography with mass spectrometry detector (12). In 2006, E. Kublin et al. have published a study on the determination of all statins by gas chromatography with FID detector (5). In 2010, a study on determination of all drugs (fibrate group) with a single column and a uniform methodology (HPLC with Symmetry C18 column and spectrophotometric detector) has been published by the same authors (17). In the Department of Basic and Applied Pharmacy, National Medicines Institute, a determination method for all statin class drugs by HPLC with Symmetry C18 column and DEVELOPMENT OF CHROMATOGRAPHIC METHOD FOR DETERMINATION OF DRUGS REDUCING CHOLESTEROL LEVEL