title: Elucidation of a CGP7930 in vitro metabolite by liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry.
abstract: BACKGROUND
  γ-Aminobutyric acid-B (GABAB ) receptors are widely expressed in the nervous system and have been implicated as targets for various neurological and psychiatric disorders. CGP7930 is a positive allosteric modulator of GABAB receptors. It has been demonstrated to reduce drug self-administration and has gained increased research as a potential psychotropic treatment.
  
  
  METHODS
  An in vitro metabolic system with liver microsomes of SD rats has been conducted and evaluated by probe drugs. The predominant in vitro metabolite of CGP7930 was identified and elucidated using liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry (LC/ESI-QTOF-MS/MS). Its structure was determined by comparing the characteristic ions of CGP7930 and those of the metabolite, based on the accurate mass measurement by MS and the fragmentation pattern obtained by MS/MS.
  
  
  RESULTS
  We found that the main metabolic pathway of CGP7930 was via a monohydroxylation reaction and the hydroxylation site located at the terminal butyl-carbon. The collision-induced dissociation (CID) fragmentation of the hydroxylated metabolite underwent McLafferty rearrangement and α-cleavage.
  
  
  CONCLUSIONS
  This work provides an understanding of the in vitro metabolism of CGP7930, which is helpful for the further study of the development of potential drug candidates targeting GABAB receptors, for the treatment of depression. The work also demonstrates that the LC/ESI-QTOF-MS/MS method has the advantage of possibly determining the structures of drug metabolites without the use of standards.
authors.affiliation: Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan, Hubei, 430074, P.R. China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan, Hubei, 430074, P.R. China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Catalysis and Materials Science of the State Ethnic Affairs Commission and Ministry of Education, College of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan, Hubei, 430074, P.R. China.
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism; D010636:Phenols / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C438607:2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)phenol; D010636:Phenols