Determination of Carvedilol in Rabbit Plasma by Gas Chromatography/ Mass Spectrometry and Its Application to Pharmacokinetic Study

Abstract

This paper describes a gas chromatography/mass spectrometry (GC/MS) method with selectedion monitoring (SIM) for the measurement of plasma carvedilol levels. Carvedilol and atenolol (internal standard, IS) were extracted from rabbit plasma with a mixture of diethyl ether and ethyl acetate at basic pH with liquid-liquid extraction. The extracts were derivatized with N-methyl-N-(trimethylsilyl)trifluoro acetamide (MSTFA) and analyzed by GC/MS. Calibration curves were linear over the concentration range 15-500 ng/mL. Intra- and inter-day precision values for carvedilol in rabbit plasma were less than 8 and accuracy (relative error) was better than 11 %. The analytical recovery of carvedilol from rabbit plasma averaged out to 88.70 %. The limit of detection (LOD) and limit of quantification (LOQ) of carvedilol were 5 and 15 ng/ mL, respectively. The developed and validated GC/MS method was also successfully applied to a pharmacokinetic study of carvedilol in New Zealand white rabbits.