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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
Author(s) -
Jiang Xiaomei,
Ling Xiaomei,
Han Fangbin,
Li Runtao,
Cui Jingrong
Publication year - 2007
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.200700081
Subject(s) - piperazine , chemistry , hydrochloride , in vivo , metabolite , ethyl ester , metabolism , chromatography , organic chemistry , biochemistry , microbiology and biotechnology , biology
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).