title: Analysis of 4-methyl-piperazine-1-carbodithioic acid 3-cyano-3,3-diphenyl-propyl ester hydrochloride and its major metabolites in rat plasma and tissues by LC-MS/MS.
abstract: 4-Methyl-piperazine-1-carbodithioic acid 3-cyano-3,3-diphenylpropyl ester hydrochloride (TM-208) is a newly synthesized compound, which has shown excellent in vivo and in vitro anticancer activity and low toxicity. To investigate the metabolism of TM-208 in rats, in the present study, we administered TM-208 orally to rats and analyzed its metabolites existing in rat plasma and central tissues by LC-MS/MS. Rat plasma and tissue samples were collected before or after a single oral dose (250 mg/kg) of TM-208, then the analytes were extracted from samples by liquid-liquid extraction and analyzed using LC-MS/MS. The structures of proposed metabolites were elucidated according to the rules of drug metabolism and disposition in vivo and the characteristic fragmentation behaviors of TM-208 in ESI-ITMS(n). Five metabolites (M1-M5) were tentatively or assuredly identified: (2-amino-ethyl)-dithiocarbamic acid 3-cyano-3,3-diphenyl-propyl ester (M1), (2-methylamino-ethyl)-dithiocarbamic acid 3-cyano-3,3-diphenyl-propyl ester (M2), 4-methyl-piperazine-1-carbothioic acid S-(3-cyano-3,3-diphenyl-propyl) ester (M3), piperazine-1-carbodithioic acid 3-cyano-3,3-diphenylpropyl ester (M4), and sulfine of (4-methyl-piperazine-1-carbodithioic acid 3-cyano-3,3-diphenylpropyl ester) (M5).
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Jiang
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Ling
authors.forename: Fangbin
authors.initials: F
authors.lastname: Han
authors.forename: Runtao
authors.initials: R
authors.lastname: Li
authors.forename: Jingrong
authors.initials: J
authors.lastname: Cui
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D002853:Chromatography, Liquid; D008297:Male; D013058:Mass Spectrometry; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014020:Tissue Extracts / Q000737:chemistry
chemical_list: C522133:4-methylpiperazine-1-carbodithioc acid 3-cyano-3,3-diphenylpropyl ester hydrochloride; D000970:Antineoplastic Agents; D010879:Piperazines; D014020:Tissue Extracts