Pharmacokinetics and tissue distribution of 4,5-dimethoxycanthin-6-one and its major metabolites in rats

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 C-18 column 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-methylcanthin2,6-dione (IS). The pharmacokinetic results indicate that 4,5-dimethoxycanthin-6-one is absorbed rapidly (T-max = 5.4-6.4 min), distributed rapidly and widely in the order of liver > kidney approximate to lungr approximate to, large intestine approximate to small intestine, and eliminated quickly (t(1/2z), = 64.9-77.7 min) following the intramuscular administration. Furthermore, M1 and M2 were detected only in rat plasma and liver at the indicated times after the intramuscular administration. (C) 2017 Elsevier B.V. All rights reserved.