Investigation of the electrochemical oxidation products of zotepine and their fragmentation using on-line electrochemistry/electrospray ionization mass spectrometry.
When zotepine, an antipsychotic drug, was electrochemically oxidized using electrospray ionization mass spectrometry (ESI-MS) coupled with a microflow electrolytic cell, [M + 16 + H]+ (m/z 348), [M-H]+ (m/z 330) and [M-14 + H]+ (m/z 318) were observed as electrochemical oxidation product ions (M represents the zotepine molecule). Although a major fragment ion that was derived from the dimethyl aminoethyl moiety was observed only at m/z 72 in the collision-induced dissociation (CID) spectrum of zotepine, new fragments such as m/z 315 and 286 ions could be generated in the CID spectrum by combining electrochemical oxidation and CID. Since these fragments were relatively specific with high ion strength, it was thought that they would be useful for developing a sensitive LC-MS/MS assay. The S-oxide and N-demethylated products were detected by electrolysis assuring that a portion of P450 metabolites of zotepine could be mimicked by the electrochemistry/electrospray ionization mass spectrometry (EC/ESI-MS) system.
Nozaki
Kazuyoshi
K
Analysis and Pharmacokinetics Research Laboratories, Astellas Pharmaceutical Inc., 1-6, Kashima 2-chome, Yodogawa-ku, Osaka 532-8514, Japan.
Kitagawa
Hiroshi
H
Kimura
Sumihisa
S
Kagayama
Akira
A
Arakawa
Ryuichi
R
D014150:Antipsychotic Agents / Q000737:chemistry* / Q000493:pharmacokinetics*; D002746:Chlorpromazine / Q000737:chemistry / Q000493:pharmacokinetics; D003988:Dibenzothiepins / Q000737:chemistry* / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation / Q000379:methods*
D014150:Antipsychotic Agents; D003988:Dibenzothiepins; C022172:zotepine; D002746:Chlorpromazine