title: Development and validation of a sensitive and robust LC-MS/MS with electrospray ionization method for simultaneous quantitation of quetiapine and its active metabolite norquetiapine in human plasma.
abstract: BACKGROUND
  Quetiapine is an atypical antipsychotic agent for the treatment of schizophrenia, acute mania, and acute bipolar depression. The antidepressive response is considered to be mediated by the metabolite norquetiapine (N-desalkylquetiapine), and the aim of this study was to develop an LC-MS/MS method to measure concentrations of these compounds in human plasma.
  
  
  METHODS
  Following one step liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a Sunfire C18 column (50mm×2.1mm, 5μm). The retention times were 2.12, 2.24, 2.12 and 2.19min for quetiapine, norquetiapine and their respective stable labeled internal standards, respectively. Cycle time was 4min. Selected reaction monitoring (SRM) in positive ion mode was used for quantitation.
  
  
  RESULTS
  The present method exhibited a linear dynamic range of 0.5-500ng/ml for quetiapine and 0.6-600ng/ml for norquetiapine. The applicable range was extended by dilution up to 5-fold with blank matrix. The accuracy and precision for quetiapine were <103.0% and 8.8%, for norquetiapine were <108.8% and 11.1%, respectively.
  
  
  CONCLUSIONS
  A rapid, sensitive, and robust LC-MS/MS method for quantifying quetiapine and its metabolite norquetiapine levels in human plasma was validated and successfully applied to samples from schizophrenic patients in clinical pharmacokinetics studies.
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing 100191, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xiong
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Jingli
authors.initials: J
authors.lastname: Duan
mesh_terms: D014150:Antipsychotic Agents / Q000097:blood; D001774:Blood Chemical Analysis / Q000379:methods*; D002853:Chromatography, Liquid; D003987:Dibenzothiazepines / Q000097:blood*; D006801:Humans; D057230:Limit of Detection; D000069348:Quetiapine Fumarate; D021241:Spectrometry, Mass, Electrospray Ionization; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; C572724:norquetiapine