Screening of Drugs and Toxic Compounds with Liquid Chromatography-Linear Ion Trap Tandem Mass Spectrometry

• Published in: Clinical chemistry (Baltimore, Md.) Md.), 2006-09, Vol.52 (9), p.1735-1742
• Main Authors: Sauvage, Francois-Ludovic, Saint-marcoux, Franck, Duretz, Benedicte, Deporte, Didier, Lachatre, Gerard, Marquet, Pierre
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Antipsychotic Agents - analysis; Antipsychotic Agents - blood; Antipsychotic Agents - urine; Biological and medical sciences; Chromatography; Chromatography, High Pressure Liquid; Forensic Medicine - methods; Fundamental and applied biological sciences. Psychology; Gas chromatography; Gas Chromatography-Mass Spectrometry; Gastrointestinal Contents - chemistry; Humans; Investigative techniques, diagnostic techniques (general aspects); Ions; Liquid chromatography; Mass spectrometry; Medical sciences; Pharmaceutical Preparations - analysis; Pharmaceutical Preparations - blood; Pharmaceutical Preparations - urine; Software; Solutions; Spectrometers; Toxicology; Xenobiotics - analysis; Xenobiotics - blood; Xenobiotics - poisoning; Xenobiotics - urine
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1373/clinchem.2006.067116

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. 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. 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. 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.