title: Screening of drugs and toxic compounds with liquid chromatography-linear ion trap tandem mass spectrometry.
abstract: BACKGROUND
  In clinical and forensic toxicology, general unknown screening is used to detect and identify exogenous compounds. In this study, we aimed to develop a comprehensive general unknown screening method based on liquid chromatography coupled with a hybrid triple-quadrupole linear ion trap mass spectrometer.
  
  
  METHODS
  After solid-phase extraction, separation was performed using gradient reversed-phase chromatography. The mass spectrometer was operated in the information-dependent acquisition mode, switching between a survey scan acquired in the Enhanced Mass Spectrometry mode with dynamic subtraction of background noise and a dependent scan obtained in the enhanced product ion scan mode. The complete cycle time was 1.36 s. A library of 1000 enhanced product ion-tandem mass spectrometry spectra in positive mode and 250 in negative mode, generated using 3 alternated collision tensions during each scan, was created by injecting pure solutions of drugs and toxic compounds.
  
  
  RESULTS
  Comparison with HPLC-diode array detection and gas chromatography-mass spectrometry for the analysis of 36 clinical samples showed that linear ion trap tandem mass spectrometry could identify most of the compounds (94% of the total). Some compounds were detected only by 1 of the other 2 techniques. Specific clinical cases highlighted the advantages and limitations of the method.
  
  
  CONCLUSIONS
  A unique combination of new operating modes provided by hybrid triple-quadrupole linear ion trap mass spectrometers and new software features allowed development of a comprehensive and efficient method for the general unknown screening of drugs and toxic compounds in blood or urine.
authors.affiliation: Department of Pharmacology-Toxicology, University Hospital, Limoges, France.
authors.forename: François-Ludovic
authors.initials: FL
authors.lastname: Sauvage
authors.forename: Franck
authors.initials: F
authors.lastname: Saint-Marcoux
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Duretz
authors.forename: Didier
authors.initials: D
authors.lastname: Deporte
authors.forename: Gérard
authors.initials: G
authors.lastname: Lachatre
authors.forename: Pierre
authors.initials: P
authors.lastname: Marquet
mesh_terms: D014150:Antipsychotic Agents / Q000032:analysis / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005554:Forensic Medicine / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry; D005766:Gastrointestinal Contents / Q000737:chemistry; D006801:Humans; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000097:blood / Q000652:urine; D012984:Software; D012996:Solutions; D015262:Xenobiotics / Q000032:analysis* / Q000097:blood / Q000506:poisoning / Q000652:urine
chemical_list: D014150:Antipsychotic Agents; D004364:Pharmaceutical Preparations; D012996:Solutions; D015262:Xenobiotics