METHODS OF CHROMATOGRAPHIC DETERMINATION OF MEDICINES DECREASING THE LEVEL OF CHOLESTEROL

Abstract

Polish Pharmaceutical Society Hyperlipidemia (HLP) is a group of disorders in the lipid balance of various pathogenesis, which demonstrate an increase in the cholesterol concentration, mostly the level of lipoprotein fractions of low density (LDL) and/or the concentration of triglycerides in blood. The increase in the total cholesterol and LDL concentration is closely connected with an increase in the risk of appearance of the cardiac ischemia and disorders in the cerebral, coronary and peripheral circulation. In May 2001, the National Cholesterol Education Program issued the third edition of the guidelines of Adult Treatment Panel (ATP III). The most important parameter of the lipid profile is the cholesterol concentration LDL ñ the proper level shall be below 130 mg/dL, though, the optimum concentration LDL has been assumed as below 100 mg/dL. The level for the cholesterol HDL has been also increased ñ the correct number shall be at the level of more than 40 mg/dL for men and more than 50 mg/dL for women and the risk factor ñ the concentration below 40 mg/dL. The third most important parameter is the concentration of triglycerides ñ the correct number shall constitute the concentration not exceeding 150 mg/dL. The selected medicines applied in the treatment of hyperlipidemia, particularily leading to a decrease in the level of cholesterol, have been apart from statins, the derivatives of aryloxyalkyl-carboxylic acids ñ so called fibrates. Fibrates inhibit the synthesis of lipoproteins VLDL in the liver and they accelerate catabolism by an increase in the activity of lipoprotein lipase. They increase the removal of fractions of the cholesterol LDL from the organism and they change their structure by means of increasing their sizes and decreasing density. Moreover, the compounds from this group influence the increase of the HDL fraction and the reverse transportation of cholesterol. The specific mechanism of action of fibrates relies on their interaction with nuclear receptors, so called PPAR (peroxisome proliferator activated receptors), which are crucial transmitters of stimuli for the genes controlling the metabolism of lipids. As a result of their action, there is a decrease in the level of triglycerides by 20ñ50%, the increase of cholesterol HDL by 10ñ15% and a decrease in the LDL fraction. Apart from the significant influence on the profile of lipids and lipoproteins, this group of com- Abstract: With reference to common application of HPLC to routine analytical tests on medicinal products decreasing the level of cholesterol, including three compounds from this group ñ fenofibrate, bezafibrate and etofibrate, we developed a new method for determining two other compounds ñ ciprofibrate and gemfibrozil. The developed HPLC method may be used for identification and qualitative determination of selected compounds ñ derivatives of aryloxyalkylcarboxylic acids as well as it may be used for simultaneous separation and determination of all compounds from the group of fibrates using one column and the same methodology. The results and statistical data indicate good sensitivity and precision. The RSD value presented is equivalent to the newly developed method of determinination of ciprofibrate and gemfibrozil in the substances and medicinal products ñ capsules and coated tablets. ANALYSIS METHODS OF CHROMATOGRAPHIC DETERMINATION OF MEDICINE