highperformance liquid chromatographymass spectrometry in the clinical laboratory the development of hplcatmospheric pressure ionizationmass spectrometry hplcms has presented clinical laboratories with a powerful analytic tool the aim of this paper is to provide an overview of the current status of hplcms 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 hplcms are neonatal screening for metabolic disorders therapeutic drug monitoring of immunosuppressant and hivaids 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 hplcms 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 trapthis 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 hplcms both of these advances in instrumentation add to the potential applications of hplcms how hplcms goes forward into the clinical laboratory is dependent on clinical scientists instrument manufacturers and regulatory authorities