The in vitro metabolism of thalicarpine, an aporphine-benzyltetrahydroisoquinoline alkaloid, in the rat. API-MS/MS identification of thalicarpine and metabolites.
The in vitro metabolism of an antitumor, hypotensive, and antimicrobial aporphine-benzyltetrahydroisoquinoline alkaloid, thalicarpine was studied after incubation with rat hepatic S9 fraction in the presence of an NADPH-generating system. Unchanged thalicarpine (46% of the sample) plus eight metabolites were profiled, quantified, and tentatively identified on the basis of API (ionspray)-MS/MS/MS data. The proposed metabolic pathways for thalicarpine are proposed, and the three metabolic pathways are: (1) N-demethylation; (2) aporphine ring oxidation; and (3) benzylic oxidation/reduction. Pathway 1 formed N-desmethyl thalicarpine (M1, 6%). Pathway 2 produced three minor keto/hydroxy metabolites (M2-M4, each 2-7%). Pathway 3 formed a major (M6, 28%) and three minor (M5, M7 and M8, each 2-3%) benzylic-cleavage metabolites. Thalicarpine is substantially metabolized by this rat hepatic system.
Wu
Wu Nan
WN
Johnson & Johnson Pharmaceutical Research and Development, LLC, Welsh and McKean Rds, PO Box 776, Spring House, PA 19477, USA. wwu@prius.jnj.com
McKown
Linda A
LA
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis* / Q000493:pharmacokinetics; D001060:Aporphines / Q000032:analysis* / Q000493:pharmacokinetics; D044182:Benzylisoquinolines; D001711:Biotransformation; D007546:Isoquinolines / Q000032:analysis* / Q000493:pharmacokinetics; D008099:Liver / Q000737:chemistry; D008297:Male; D008745:Methylation; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013347:Subcellular Fractions / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D001060:Aporphines; D044182:Benzylisoquinolines; D007546:Isoquinolines; C073328:thalicarpine