Premium
The identification of in vitro metabolites of bupropion using ion trap mass spectrometry
Author(s) -
Taylor Lester C. E.,
Singh Rominder,
Chang Sai Y.,
Johnson Robert L.,
Schwartz Jae
Publication year - 1995
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.1290091008
Subject(s) - chemistry , mass spectrometry , chromatography , atmospheric pressure chemical ionization , ion trap , s9 fraction , fragmentation (computing) , quadrupole ion trap , orbitrap , analytical chemistry (journal) , ion , chemical ionization , microsome , ionization , in vitro , biochemistry , organic chemistry , computer science , operating system
We have identified in vitro metabolites of bupropion (Wellbutrin®) from incubations with human liver S9 fraction and human liver microsomes based on molecular weight information from full scan experiments using a liquid chromatograph coupled to a quadrupole ion trap mass spectrometer capable of multi‐stage operation (LC/MS n ). Preliminary experiments have shown that this instrument provides comparable sensitivity to conventional LC‐coupled triple quadrupole instruments for metabolic studies, while allowing detailed structural studies using MS n experiments and routine on‐line coupling with high performance liquid chromatography via an external atmospheric pressure chemical ionization (APCI) source. The LC/MS analysis of human S9 showed the presence of three isomeric monohydroxylated metabolites of bupropion. These were further characterized in a series of MS/MS experiments which gave characteristic spectra for the three isomers. A minor dihydroxylated species was also identified in the human S9 sample and further characterized in a series of MS n experiments. Detailed structural information was generated by the use of on‐line LC/MS n type experiments. We have followed the fragmentation pathways of several molecular ion species in a series of sequential LC/MS n experiments, extending as far as MS 6 with scan cycle times of less than 1.5 s. Such experiments have provided insights into the structure of specific fragment ions. Additional metabolic products were identified in the rat liver microsomes incubation sample.