title: Studies on the metabolism of 4-methyl-piperazine-1-carbodithioc acid 3-cyano-3,3-diphenylpropyl ester hydrochloride in rats by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.
abstract: 4-Methyl-piperazine-1-carbodithioc acid 3-cyano-3,3-diphenylpropyl ester hydrochloride(TM208) is a newly synthesized compound, which has shown excellent in vivo and in vitro anticancer activity and low toxicity. In this study, the metabolism of TM208 in rats was studied for the first time by high-performance liquid chromatography coupled with tandem mass spectrometry. Following a single oral administration to rats, TM208 was metabolized to eight metabolites (M1-M8). M1 is the desmethyl metabolite and the acylation of M1 with N-acetyl transferase results in M6 (N-acetyl metabolite), M5 is N-formyl metabolite; M4 is phenyl monohydroxylation metabolite, M2 is the sulfine metabolite of TM208, and M3 is also an odd-oxygen added products which the possible oxidation site has described in this paper; M8 is the metabolite resulting from the replacement of '-C=S' with '-C=O', M7 is a ring-opened piperazine oxidation products to a kind of acid.
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing 100083, 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: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005243:Feces / Q000737:chemistry; D008297:Male; D015394:Molecular Structure; D010879:Piperazines / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: C522133:4-methylpiperazine-1-carbodithioc acid 3-cyano-3,3-diphenylpropyl ester hydrochloride; D000970:Antineoplastic Agents; D010879:Piperazines