High-performance liquid chromatography-mass spectrometry in the clinical laboratory

The development of HPLC-atmospheric pressure ionization-mass spectrometry (HPLC-MS) has presented clinical laboratories with a powerful analytic tool. The aim of this paper is to provide an overview of the current status of HPLC-MS in the clinical laboratory; to discuss the challenges to mass spectrometry in this setting; and to present some of the latest developments in instrumentation and illustrate their potential application. Currently, the major clinical applications for HPLC-MS are neonatal screening for metabolic disorders, therapeutic drug monitoring of immunosuppressant and HIV/AIDS drugs, and toxicological investigations. The major barrier to the uptake of this technology in the clinical laboratory is the initial capital outlay for instrumentation. A secondary reason is the lack of suitably trained scientists. The challenges that clinical HPLC-MS face are (I) ease of use and automation, (2) interpatient variability in relation to matrix effects, (3) availability of suitable internal standards, and (4) harmonization of methods to meet regulatory requirements. The development of the triple quadrupole linear ion trap mass analyzer allows the quantification power of a triple quadrupole mass analyzer to be combined with the scanning ability of an ion trap.This hybrid instrument allows different permutations of scan combinations. The combination of selected reactant monitoring and MS3 is an attractive combination for quantification. The ion source, atmospheric pressure photoionization, has recently been developed and is well suited to nonpolar analytes, although its role is yet to be established. This ion source complements other interfaces used in HPLC-MS. Both of these advances in instrumentation add to the potential applications of HPLC-MS. How HPLC-MS goes forward into the clinical laboratory is dependent on clinical scientists, instrument manufacturers, and regulatory authorities.