Pitfalls and Prevention Strategies for Liquid Chromatography-Tandem Mass Spectrometry in the Selected Reaction- Monitoring Mode for Drug Analysis

We observed cases of false-positive results with the use of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Different LC-MS/MS techniques that use the selected reaction-monitoring mode, routinely employed for the analysis and quantification of drugs and toxic compounds in bio...

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Bibliographic Details
Published in:Clinical chemistry (Baltimore, Md.) Md.), 2008-09, Vol.54 (9), p.1519-1527
Main Authors: Sauvage, Francois-Ludovic, Gaulier, Jean-Michel, Lachatre, Gerard, Marquet, Pierre
Format: Article
Language:English
Subjects:
Analytical, structural and metabolic biochemistry
Atropine - chemistry
Atropine - urine
Biological and medical sciences
Chromatography
Chromatography, Liquid - methods
Clomipramine - analysis
Clomipramine - metabolism
Date rape
Drugs
Fundamental and applied biological sciences. Psychology
Humans
Investigative techniques, diagnostic techniques (general aspects)
Liquid chromatography
LSD
Lysergic acid diethylamide
Lysergic Acid Diethylamide - chemistry
Lysergic Acid Diethylamide - urine
Mass spectrometry
Medical sciences
Metabolites
Methods
Molecular Structure
Pharmaceutical Preparations - analysis
Pharmaceutical Preparations - chemistry
Phenothiazines - analysis
Phenothiazines - metabolism
Relative abundance
Tandem Mass Spectrometry - methods
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Summary:We observed cases of false-positive results with the use of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Different LC-MS/MS techniques that use the selected reaction-monitoring mode, routinely employed for the analysis and quantification of drugs and toxic compounds in biological matrices, were involved in the false-positive and potentially false-positive results obtained. We sought to analyze the causes of and solutions to this problem. We used a previously reported LC-MS/MS general unknown screening method, as well as manual spectral investigation in 1 case, to perform verification and identification of interfering compounds. We observed that false-positive results involved: a metabolite of zolpidem that might have been mistaken for lysergic acid diethylamide, benzoylecgonine mistaken for atropine, and clomipramine and 3 phenothiazines that share several common ion transitions. To prevent problems such as those we experienced, we recommend the use of stable-isotope internal standards when possible, relative retention times, 2 transitions or more per compound when possible, and acceptable relative abundance ratios between transitions, with an experience-based tolerance of +/-15% for transitions with a relative abundance >10% and with an extension to +/-25% for transitions
ISSN:0009-9147
1530-8561
DOI:10.1373/clinchem.2008.105478