Fiber-Based Liquid-Phase Micro-Extraction of Mebeverine Enantiomers Followed by Chiral High-Performance Liquid Chromatography Analysis and Its Application to Pharmacokinetics Study in Rat Plasma

The applicability of two-phase liquid-phase micro-extraction (LPME) in porous hollow polypropylene fiber for the sample preparation and the stereoselective pharmacokinetics of mebeverine (MEB) enantiomers (an antispasmodic drug) in rat after intramuscular administration were studied. Plasma was assayed for MEB enantiomer concentrations using stereospecific high-performance liquid chromatography with ultraviolet detection after a simple, inexpensive, and efficient preconcentration and clean-up hollow fiber-based LPME. Under optimized micro-extraction conditions, MEB enantiomers were extracted with 25?mu l of 1-octanol within a lumen of a hollow fiber from 0.5?ml of plasma previously diluted with 4.5?ml alkalized water (pH 10). The chromatographic analysis was carried out through chiral liquid chromatography using a DELTA S column and hexaneisopropyl alcohol (85:15?v/v) containing 0.2% triethylamine as mobile phase. The mean recoveries of (+)-MEB and (-)-MEB were 75.5% and 71.0%, respectively. The limit of detection (LOD) was 3.0?ng/ml with linear response over the concentration range of 102500?ng/ml with correlation coefficient higher than 0.993 for both enantiomers. The pharmacokinetic studies showed that the mean plasma levels of (+)-MEB were higher than those of (-)-MEB at almost all time points. Also, (+)-MEB exhibited greater tmax (peak time in concentrationtime profile), Cmax (peak concentration in concentrationtime profile), t1/2 (elimination half-life), and AUC0240?min (area under the curve for concentration versus time) and smaller CL (clearance) and Vd (apparent distribution volume) than its antipode. The obtained results implied that the absorption, distribution, and elimination of (-)-MEB were more rapid than those of (+)-MEB and there were stereoselective differences in pharmacokinetics. Chirality 24:634639, 2012. (c) 2012 Wiley Periodicals, Inc.