Analysis of five HMG‐CoA reductase inhibitors— atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin: pharmacological, pharmacokinetic and analytical overview and development of a new method for use in pharmaceutical formulations analysis and in vitro metabolism studies

Abstract

A specific, accurate, precise and reproducible high-performance liquid chromatographic (HPLC) method was developed and validated for the simultaneous quantitation of five 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, viz. atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin, in pharmaceutical formulations and extended the application to in vitro metabolism studies of these statins. Ternary gradient elution at a flow rate of 1 mL/min was employed on an Intertisl ODS 3V column (4.6 x 250 mm, 5 microm) at ambient temperature. The mobile phase consisted of 0.01 m ammonium acetate (pH 5.0), acetonitrile and methanol. Theophylline was used as an internal standard (IS). The HMG-CoA reductase inhibitors and their metabolites were monitored at a wavelength of 237 nm. Drugs were found to be 89.6-105.6% of their label's claim in the pharmaceutical formulations. For in vitro metabolism studies the reaction mixtures were extracted with simple liquid-liquid extraction using ethyl acetate. Baseline separation of statins and their metabolites along with IS free from endogenous interferences was achieved. Nominal retention times of IS, atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin were 7.5, 17.2, 21.6, 28.5, 33.5 and 35.5 min, respectively. The proposed method is simple, selective and could be applicable for routine analysis of HMG-CoA reductase inhibitors in pharmaceutical preparations as well as in vitro metabolism studies.

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

“…Far to our knowledge first HPLC-PDA method for simultaneous analysis of atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin was reported for determination in pharmaceutical formulations and in vitro metabolism studies [121]. An uncommon gradient method using 3 mobile phase reservoirs was employed.…”

Method Validation for Analysis of Simvastatin in Human Plasma Using Liquid Chromatography Tandem Mass Spectrometry (LC-MS-MS)

“…Since plasma concentrations of simvastatin is expected to be between 0.1 and 15 ng/mL [12]. However, method by HPLC-UV is suitable for determining simvastatin in pharmaceutical formulations and preparations [13], but is not suitable for pharmacokinetic study. Therefore, sensitive and selective methods for the determination of simvastatin are required for therapeutic drug level monitoring.…”

Effects of bile salts on the lovastatin pharmacokinetics following oral administration to rats

“…It is synthesized from Asperigillus terreus and is an inactive prodrug that is converted to ß-hydroxylate by the liver (Endo, 1981;Sirtori, 1990). It is highly effective in reducing apolipoprotein-B-containing lipoproteins, especially low-density lipoprotein cholesterol and, to a lesser extent, plasma triglycerides, and may cause a small increase in high-density lipoprotein cholesterol (Tobert, 2003;Pasha et al, 2006).…”