Development of screening procedures using liquid chromatography-tandem mass spectrometry for forensic and clinical application ; Mise au point de méthodes de recherche large de xénobiotiques par chromatographie liquide couplée à la spectrométrie de masse en tandem

Screening methods for compounds of interest in clinical toxicology have been historically employed as first-line analysis to either confirm or exclude the hypothesis of drug overdose, or poisoning with a toxicant. After identification using a screening method, quantification using specific methods is often necessary in a second time to assess the severity of intoxication. This obviously increases the turnaround time and has an impact on patient care. With regards to the rapidity needed to report results in clinical toxicology, sample extraction may be a limiting step. There is no universal extraction procedure for human samples prior to screening analysis Our goal were to developed screening procedures using a programmable liquid handler (CLAM-2000; Shimadzu®) directly coupled to a liquid chromatography - tandem mass spectrometry (LC-MS 8060; Shimadzu®).Libraries with spectral and chromatographic parameters were built for about 1300 compounds selected based on their relevance to, and occurrence in, clinical toxicology. Using these libraries, screening methods were developed using different acquisition modes.Two different extraction procedures were developed: one using QuEChERS salts, another using the CLAM-2000.Each approach was validated according to the ISO 15189 requirements and was applied to real patient samples. The different screening methods yielded high confidence in compound detection and should be useful in core labs facing clinical toxicology situations where rapid and reliable results are needed. ; Dans de nombreux contextes de toxicologie clinique, le screening ou criblage toxicologique est la première analyse effectuée chez un patient, lorsque la nature ou la présence même de médicaments ou de toxiques est totalement inconnue. Le plus souvent, le screening précède la mise en œuvre de méthodes quantitatives spécifiques. Les méthodes d’extractions peuvent être diverses mais celles-ci restent en général manuelles.Les objectifs de nos travaux étaient de développer des méthodes de screening ...