Liquid chromatography-mass spectrometry: potential in forensic and clinical toxicology

A relatively limited number of papers concerning applications of liquid chromatography-mass spectrometry (LC-MS) to forensic or clinical toxicology, or analytical methods directly applicable to these topics have been published so far, but their number have greatly increased in the past two years, probably due to technical improvements and to a decrease in the price of such instruments. After a brief presentation and exemplary applications of the interfaces and/or sources proposed in the past for coupling HPLC to mass spectrometry (direct liquid inlet, moving belt, fast atom bombardment and thermospray interfaces), this paper describes electrospray-type and atmospheric pressure chemical ionisation interfaces and their most recent applications in forensic or clinical toxicology. In a third section, the different LC-MS solutions proposed for typical applications in human toxicology, such as the determination of morphine metabolites, LSD and its metabolites and corticosteroids in blood or urine, are reviewed in detail in order to highlight the strengths and weaknesses of each ionisation device and/or analytical method. The last section envisages the new analytical fields opened up by LC-MS in toxicology, regarding mainly peptides, proteins and large molecules, as well as the possible use of LC-MS as a complement to GC-MS for "general unknown" screenings; it also deals with the perspectives concerning technical improvements in ionisation interfaces/sources or mass spectrometers, as well as in sample preparation and liquid chromatography techniques applied to this type of coupling. Though LC-MS is still a relatively new technique in toxicology, on taking into consideration its success so far and owing to the simplification of instruments and concept handling thanks to user-friendly software, it is the authors' opinion that it will become a major success in analytical toxicology in the next few years.