title: Development and validation of a chiral liquid chromatography method for the determination of MP 3950 enantiomers, a high selective 5-HT4 receptor agonist, in rat plasma and its application to stereoselective pharmacokinetic study.
abstract: MP 3950 is an active metabolite of mosapride which exhibits high 5-HT4 receptor agonistic effect. The present paper describes an enantioselective chiral HPLC method for separation and quantification of MP 3950 enantiomers in rat plasma. The plasma samples were prepared by liquid-liquid extraction with ethyl acetate and the baseline chromatographic separation was achieved on a Chiralcel OJ-H column with a mobile phase consisting n-hexane/ethanol/methanol/diethylamine (85:5:10:0.4, v/v/v/v) at the flow rate of 1.0mL/min. The ultraviolet detection was performed at 276nm. The calibration curve was linear in the range from 0.100 to 5.00μg/mL with the lower limit of quantification of 0.100μg/mL for each enantiomer. The intra- and inter-day precisions were not more than 14.7%. The accuracy was from -6.4% to 14.0%. The validated method was successfully applied to chiral inversion and stereoselective pharmacokinetic study in rats after oral administration of MP 3950 racemate. The results indicated that no stereochemical inversion was occurred in rats. And the plasma concentrations and area under plasma concentration-time curve of (S)-MP 3950 were all significantly higher than those of (R)-MP 3950 in both male and female rats, which indicated that the disposition of MP 3950 in rats might be stereoselective.
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors: Chengying
authors: C
authors: Wang
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors: Hong
authors: H
authors: Sun
authors: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China.
authors: Shaojie
authors: S
authors: Wang
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors: Zhonggui
authors: Z
authors: He
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors: Longshan
authors: L
authors: Zhao
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: bearry200@126.com.
authors: Zhili
authors: Z
authors: Xiong
authors: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: qf-1998@163.com.
authors: Feng
authors: F
authors: Qin
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001549:Benzamides / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D057230:Limit of Detection; D008297:Male; D009025:Morpholines / Q000378:metabolism; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D058828:Serotonin 5-HT4 Receptor Agonists / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D013237:Stereoisomerism
chemical_list: D001549:Benzamides; D009025:Morpholines; D058828:Serotonin 5-HT4 Receptor Agonists; C062720:mosapride
keywords: Chiral HPLC; Chiral inversion; Enantiomer separation; MP 3950; Stereoselective pharmacokinetics