A decade of HPLC–MS/MS in the routine clinical laboratory — Goals for further developments

During the past decade, tandem mass spectrometry hyphenated to liquid chromatography separation systems (HPLC-MS/MS) has developed to an important technology in clinical chemistry - not only for research purposes but also for routine use. At present, most important application fields are target analyses in therapeutic drug monitoring (TDM) and metabolic disorders diagnosis. The essential strengths of HPLC-MS/MS include potentially high analytical specificity, wide range of applicability to small and large molecules, capability of multi- and mega-parametric tests, and the opportunity to develop powerful assays with a high degree of flexibility within a short time frame. The technique has overcome important limitations of GC-MS and is characterized by short analytical runtimes, applicability to thermo labile, polar and large molecules, and straightforward sample preparation. However, implementation of HPLC-MS/MS assays still requires substantial expertise and know-how. At the present, its application is limited to a rather small number of clinical routine laboratories. Nonetheless, HPLC-MS/MS has the potential to be further developed to a commonly applied high-throughput technique in clinical chemistry, complementary to present standard techniques as photometry and ligand binding methods. This review intends to characterize working characteristics of present day HPLC-MS/MS instrumentations used in clinical routine laboratories. Limitations of currently available systems and applications will be critically discussed. Required instrument improvements supporting the successful spreading of HPLC-MS/MS in laboratory medicine within the next decade will be outlined.