Mass spectrometry in laboratory medicine: When "high-tech" meets routine needs.

Accessibility to liquid chromatography coupled tomass spectrometry (LC-MS) as analytical for biological analysis increased in the 1990s, to emerge in clinical laboratories at the beginning of the 21st Century. It had soon become evident that this technology had several advantages over the HPLC and GC-MS techniques. Samples extraction and pretreatment were simpler, run-times shorter, and selectivity appeared so high that a careful chromatographic separation was, at one point, even considered in some instances an unnecessary step. The application of LC coupled to (tandem) mass spectrometry [LC-MS (MS)] applied to the analysis of small and large molecules, and of thermo-labile or polar compounds led it to be rapidly considered a quasi-universal method that rapidly became adopted by clinical laboratories. The Tacrolimus International Proficiency Testing Scheme (http://www.bioanalytics.co. uk/) survey illustrates the progression of the use of this technology. Whereas in 1999 only 2% of the surveyed laboratories used LC-MS, 27% of them have integrated it in 2010 [1]. Besides industrial applications, LC-MS (MS) was initially limited to neonatal screening and toxicology/ therapeutic drug monitoring. However, more recently, with the improvement in the technologies and informatics, newer applications have been developed to address clinical problems in endocrinology (steroids, thyroid hormones), metabolism (biogenic amines, small peptides), and nutrition (vitamins, nutriceutics). More remarkably, spectacular progress in computer sciences and in MALDI-TOF technology has opened unexpectedfields for clinicalmass spectrometry such as microbiology, proteomics, metabolomics, etc. Undoubtedly, large-scale mass-spectrometric-based screening will identify new biomarkers for pathologies and for patient treatment follow-up. Some factors however attenuate the initial enthusiasm for this promising technology. The increased economic pressure that characterized the last decade in many countries led to obligatory laboratory consolidation and mergers, resulting in fewer but larger medical laboratories. Such a trend was favourable to the development of mass spectrometry techniques that require large series of analyses to reach profitability. Although the initial investment in equipment can be amortized through a reduction of the global reagents costs when shifting away from immunoassays, it remains one of the limitations to a wider use of this technology. Unavailability of technical and analytical expertise, and absence of a 24 h/day and a 7 days a week support by manufacturers are also limitations to a wider use of this technology. As this is recognized by the manufacturers, efforts are being made to provide increased automation and support in the near future. Caution should also be observed when considering the use of LC-MS (MS). Indeed, the major improvements in its ease of use has blurred the fact that it remains within the realm of high technology that involves ionisation and fragmentation processes requiring expert analysis to avoid misleading interpretation. Also, temptation is great for laboratory and hospital administrators tobelieve that theuser-friendliness of themodern