title: Metabolism of 6-chloro n-butyl phthalide in rat.
abstract: 6-Chloro n-butyl phthalide (CBP) was orally administered to healthy, male Wistar rats pretreated with or without 3-methylcholanthrene (3-MC) by a single dose of 150 mg/kg, and urine samples were collected for 0-24 h. The urine sample was hydrolyzed with beta-glucuronidase, extracted and concentrated for TMS derivatization, and analysed on a GC-MS system for identification of CBP metabolities. Mass spectral analysis suggests that 7 CBP metabolites were present in the urine sample, and similar metabolism patterns were viewed in rats with or without pretreatment with 3-MC. Four main metabolites of CBP in rat urine were identified as alpha-beta oxolate, beta-gamma oxolate, beta-hydroxylate and gamma-hydroxylate, based on their chromatographic and mass spectral properties. Two hydroxylates have been previously identified in CBP metabolism by rat liver microsomes. The other two metabolites with higher polarity were tentatively identified as dihydroxylation products on the n-butyl side chain by the mass spectra of their TMS derivatives. One minor metabolite was found by the isotopic effect of chlorine, but its specific structure was undetermined. The difference between in vivo and in vitro metabolic profiles of CBP is also discussed.
authors.affiliation: Department of Analytical Chemistry, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: S H
authors.initials: SH
authors.lastname: Peng
authors.forename: T H
authors.initials: TH
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism*; D001572:Benzofurans / Q000138:chemical synthesis / Q000378:metabolism* / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D005966:Glucuronidase; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: C106182:6-chloro-butyl-phthalide; D000927:Anticonvulsants; D001572:Benzofurans; D005966:Glucuronidase