title: Pharmacokinetics and tissue distribution of 4,5-dimethoxycanthin-6-one and its major metabolites in rats.
abstract: 4,5-Dimethoxycanthin-6-one and 5-hydroxy-4-methoxycanthin-6-one are the active ingredients of P. quassiodes. In the present work, a LC-MS/MS method was developed for the determination of 4,5-dimethoxycanthin-6-one and its major metabolites 5-hydroxy-4-methoxycanthin-6-one (M1) and 4-hydroxy-5-methoxycanthin-6-one (M2) in rat plasma and tissues, and applied to study their pharmacokinetics and tissue distribution after intramuscular administration of 4,5-dimethoxycanthin-6-one to rats. By protein precipitation with methanol for plasma samples and liquid-liquid extraction with ethyl acetate for tissue samples, the analytes were separated on an ODS C18column with a mobile phase consisted of methanol and water (0.1% formic acid), and quantified by a MS detector in positive multiple reaction monitoring (MRM) mode. MS transitions were m/z 281.0→167.1 for 4,5-dimethoxycanthin-6-one, m/z 267.0→168.1 for M1 and M2, m/z 251.0→195.1 for 3-methylcanthin-2,6-dione (IS). The pharmacokinetic results indicate that 4,5-dimethoxycanthin-6-one is absorbed rapidly (Tmax=5.4-6.4min), distributed rapidly and widely in the order of liver>kidney≈lung≈large intestine≈small intestine, and eliminated quickly (t1/2z=64.9-77.7min) following the intramuscular administration. Furthermore, M1 and M2 were detected only in rat plasma and liver at the indicated times after the intramuscular administration.
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei University, Wuhan 430062, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Miao
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei University, Wuhan 430062, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Hubei Province Key Laboratory of Biotechnology of Chinese Traditional Medicine, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei University, Wuhan 430062, China. Electronic address: cy101610@qq.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D002243:Carbolines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D008297:Male; D032270:Picrasma; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
chemical_list: D002243:Carbolines; D004365:Drugs, Chinese Herbal; C468517:5-methoxycanthin-6-one
keywords: 4,5-Dimethoxycanthin-6-one; LC–MS/MS; Metabolites; Pharmacokinetics; Tissue distribution