Studies on the metabolism of 4-methylpiperazine-1-carbodithioc acid 3-cyano-3,3- diphenylpropyl ester hydrochloride in rat bile by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry

4‐Methylpiperazine‐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 the present study, the major metabolites of TM208 in rat bile were studied by high‐performance liquid chromatography/tandem mass spectrometry with an electrospray ionization (ESI) interface. It was demonstrated that TM208 was extensively metabolized in rat bile and nine metabolites (M1–M9) were definitely or tentatively identified: (2‐aminoethyl)dithiocarbamic acid 3‐cyano‐3,3‐diphenylpropyl ester (M1), (2‐methylaminoethyl)dithiocarbamic acid 3‐cyano‐3,3‐diphenylpropyl ester (M2), 4‐[(4‐methylpiperazin‐1‐yl)thioxomethanesulfinyl]‐2,2‐diphenylbutyronitrile (M3), 4‐methylpiperazine‐1‐carbodithioic acid 3‐cyano‐3‐(4‐hydroxyphenyl)‐3‐phenylpropyl ester(M4), the sulfine of (4‐methylpiperazine‐1‐carbodithioc acid 3‐cyano‐3,3‐diphenylpropyl ester) (M5), 4‐methylpiperazine‐1‐carbothioic acid S‐(3‐cyano‐3,3‐diphenylpropyl) ester (M6), piperazine‐1‐carbodithioic acid 3‐cyano‐3,3‐diphenylpropyl ester (M7), 4‐hydroxymethylpiperazine‐1‐carbothioic acid S‐(3‐cyano‐3,3‐diphenylpropyl) ester (M8) and the sulfine of [4‐methylpiperazine‐1‐carbodithioic acid 3‐cyano‐3‐(4‐hydroxyphenyl)‐3‐phenylpropyl ester] (M9). Copyright © 2007 John Wiley & Sons, Ltd.