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Characterization of in vitro metabolites of the antipsychotic drug tiospirone by mass spectrometry
Author(s) -
Jajoo Hemant K.,
Blair Ian A.,
Klunk Lewis J.,
Mayol Robert F.
Publication year - 1990
Publication title -
biomedical and environmental mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 0887-6134
DOI - 10.1002/bms.1200190502
Subject(s) - chemistry , hydroxylation , chromatography , mass spectrometry , metabolite , gas chromatography–mass spectrometry , glucuronide , chemical ionization , gas chromatography , microsome , organic chemistry , ion , biochemistry , ionization , enzyme
Metabolism of the antipsychotic drug tiospirone was studied in vitro with phenobarbital‐induced rat liver microsomes. Metabolites were isolated and purified to homogeneity by high‐performance liquid chromatography. It was possible to characterize the metabolites as trimethylsilyl (TMS) derivatives by gas chromatography/electron impact mass specrometry (GC/EIMS) so long as the sulfur was present in the reduced form. However, sulfoxide and sulfone analogs of tiospirone underwent reductive decomposition on the GC column. In addition, no molecular ions were observed in the EI spectra of these analogs. Desorption chemical ionization/mass spectrometry (DCI/MS) in the positive ion mode with methane as reagent gas successfully distinguished sulfoxides and sulfones from their parent sulfides. Protonated molecular ions were observed together with structurally significant fragment ions. Five microsomal metabolites of tiospirone were characterized by a combination of GC/EIMS and DCI/MS. From the structures of the metabolites three major pathways of metabolism were identified: N ‐dealkylation of the butyl side chain at the piperazinyl nitrogen, hydroxylation α to the glutarimidyl carbonyl at C‐6 on the azaspirodecanedione ring, and sulfoxide formation on the benzisothiazole moiety.