Determination of the HMG-CoA reductase inhibitors simvastatin, lovastatin, and pravastatin in plasma by gas chromatography/chemical ionization mass spectrometry

Abstract

A general method for the assay of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors lovastatin, pravastatin, and simvastatin in plasma has been developed and validated. The analytes are isolated from plasma by a solid-phase extraction procedure which separates the lactone and acid forms of the drugs. The lactone is converted to the acid form, which is subsequently derivatized by pentafluorobenzylation of the carboxyl group, and trimethylsilylation of the hydroxyl functions. Derivatized samples of intrinsic and converted acid are assayed by gas chromatography/mass spectrometry using negative chemical ionization mass spectrometry. The method has sufficient sensitivity, precision, accuracy, and selectivity for the analysis of clinical samples containing the drugs administered at therapeutic doses. The method thus permits determination of both the lactone and hydroxy acid forms of lovastatin and simvastatin, and is also applicable to the assay of pravastatin.

A Simple and Sensitive HPLC-UV Method for Quantitation of Lovastatin in Human Plasma: Application to a Bioequivalence Study

“…Although a series of sensitive and accurate methods have been described for determination of lovastatin in biological fluids, but all these methods require the use of sophisticated and relatively non-popular instrumentations such as gas chromatography/mass spectrometry [5][6][7] or, more recently, highperformance liquid chromatography/mass spectrometry, 8,9) the availability of a simple, popular and cost-effective method for this purpose remains a limiting factor against pharmacokinetic studies on this drug. The purpose of this investigation was to develop a rapid, popular, and sensitive analytical method, based on HPLC with UV detection of lovastatin in human plasma in order to, primarily, be used throughout a bioequivalence study.…”

Stability indicating LC-MS/MS method for estimation of lovastatin in human plasma: application to a bioequivalence study

“…In the reported gas chromatography-mass spectrometric method (Morris et al 1993), the sensitivity was improved by derivatization, but it is a timeconsuming process. LC-MS/MS methods (Dong et al 2008;Haiyan et al 2008;Lin et al 2008;Nageswararao et al 2012;Ramakrishna et al 2007;Xiao et al 2006;Xiu and Chris 2003;Wu et al 1997) have also been reported with increased sensitivity but the inter-conversion between lovastatin to lovastatin hydroxy acid has not been studied in these methods, which could lead to pseudo estimation of lovastatin in plasma.…”

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

“…Recently, numerous methods for analysis of simvastatin and its metabolites determination in human plasma by HPLC methods with difference detectors (ultraviolet, fluorescence and mass spectrometry) have been published [4][5][6][7][8][9]. In addition, some methods of gas chromatography with mass spectrometry for determination of simvastatin and its metabolites have also been published [10][11]. However, most of these methods are tedious and time consuming, which also considered costly for routine analysis work.…”