title: Biosynthesis and stereoselective analysis of (-)- and (+)-zaltoprofen glucuronide in rat hepatic microsomes and its application to the kinetic analysis.
abstract: Zaltoprofen, available commercially as a racemic mixture, is a propionic acid derivative of non-steroidal anti-inflammatory drugs (NSAIDs). Firstly, (+)- and (-)-zaltoprofen glucuronide was biosynthesized and purified. Then a simple and rapid RP-HPLC analysis method for direct determination of (+)- and (-)-zaltoprofen glucuronide in rat hepatic microsomes was developed and validated. The calibration curves of (+)- and (-)-zaltoprofen glucuronide both showed good linearity in the concentration range from 0.15 to 31.13 μM. The lower limit of quantification was 0.15 μM. Finally, this method was used to investigate the enantioselectivity of zaltoprofen glucuronidation in rat hepatic microsomes. The kinetics of zaltoprofen glucuronidation in rat hepatic microsomes for 40 min incubation fit the Michaelis-Menten model. Kinetic analysis indicated that (-)-zaltoprofen had a higher glucuronidation rate in rat liver microsome than that of (+)-zaltoprofen. The catalyzing efficiency (V(max)/K(m)) ratio of (+)-zaltoprofen to (-)-enantiomer is 0.8 times in rat liver microsomes.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang Province, China.
authors.forename: Haina
authors.initials: H
authors.lastname: Wang
authors.forename: Jianbo
authors.initials: J
authors.lastname: Ji
authors.forename: Su
authors.initials: S
authors.lastname: Zeng
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D020719:Glucuronides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000737:chemistry / Q000378:metabolism*; D011422:Propionates / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D020719:Glucuronides; D011422:Propionates; C043940:pyranoprofen