Investigation of the electrochemical oxidation products of zotepine and their fragmentation using on‐line electrochemistry/electrospray ionization mass spectrometry

Abstract

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.

Application of On-line Electrochemistry/Electrospray/Tandem Mass Spectrometry to a Quantification Method for the Antipsychotic Drug Zotepine in Human Serum

“…Although an electrolytic microflow cell was used in our previous study, 6 an ESA coulometric cell was selected for this study, because a microflow cell is vulnerable to the high pressure of an HPLC column. The optimal voltage of the ESA electrochemical cell was investigated by flow injection of the zotepine standard solution mixed with the HPLC mobile phase through a three-way union before reaching the EC cell.…”

“…The product ion at m/z 232 is probably generated by cleavage of the N-dimethyl amino moiety, like that at m/z 303 from the electrochemical S-oxidation of zotepine. 6 …”

“…4,5 Our previous study revealed that new fragment ions that allow a sensitive quantification of zotepine are formed by combining on-line EC/ESI-MS and collision-induced dissociation (CID). 6 The electrochemical product ion of [M-H] + (m/z 330) was detected, and yielded new fragment ions, such as m/z 315 and 286 ions, in the CID spectrum, while there was only one major fragment ion at m/z 72 in the CID spectrum of zotepine with ordinary ESI-MS/MS, derived from the cleaved side-chain moiety. It has been particularly difficult to use this fragment (m/z 72) with an ion-trap mass spectrometer, owing to a restriction on the lower limit of detectable fragment ions.…”

High Performance Liquid Chromatography/Electrochemistry/High Resolution Electrospray Ionization‐Mass Spectrometry (HPLC/EC/HR ESI‐MS) Characterization of Selected Cytokinins Oxidation Products

“…À2H iP has been investigated and fragmentation data are provided [19] -iA and iE structures were made solely on this base, as the mass of in-source fragmentation ions leaves no other option than the dehydrogenation of the side-chain and therefore matching the structures with [19]. Dehydrogenation of aliphatic chain has been directly performed by EC [20]. iA and iE are tautomers, assigning the two possible structures to their two largely differing elution times was made by presuming that the exposed double bond in iA is responsible for increased polarity and thus shorter retention time.…”

MECHANISTIC STUDY OF COLCHICINE’s ELECTROCHEMICAL OXIDATION

“…Since its first report in 1971 [35], the on-line EC/MS coupling was predominantly exploited for the identification of the emerging stable and/or transient (radical-cation or radical-anion) reaction products [36][37][38][39]. Nowadays, EC/MS grew into a powerful technology of wide applicability, such as: signal enhancement in MS, proteomics, study of DNA damage, testing of cosmetics on skin sensitizing effects, predicting the degradation and persistence of pollutants, and last, but not least, mimicking drug and xenobiotic metabolism [40,41].…”