In the clinical routine lab, only a small number of diagnostic tests are currently available for peptides and proteins, compared with the large number of proteins available in the blood and the multitude of potential biomarkers. Laboratory diagnostics is dominated by the application of immunoassays and enzymatic tests. Despite a number of limitations such as single parameter analysis and cross-reactivity, there is currently no alternative as they are available on full laboratory automation 24h a day, 7 days a week. The concept of quantifying proteins via proteotypic peptides by coupling liquid chromatography and tandem mass spectrometry has been recently successfully developed for simultaneous quantification of proteins from blood but also for phenotyping. In addition to its application in biomarker studies, this principle also has great potential for routine diagnostics. The combined quantification of apolipoproteins with Apo E phenotyping and the analysis of abnormal haemoglobin variants in newborn screening are applications that are already established or on the way to routine applications. With these two examples the principle of quantitative mass spectrometric analysis of proteins for use in clinical routine analysis will be presented and its further perspectives critically discussed.

Mass spectrometry (MS) hyphenated to high-resolution separation techniques, especially LC and GC, is a well-established key technology in clinical routine and research. In addition, MS based readouts from complex instrumental analysis measurement systems can serve as the rational basis for reference measurement procedures and services. Key to this successful application is the high selectivity of mass spectrometry-based ion current readouts, especially if selected reaction monitoring (SRM) experiments or high-resolution detector systems are employed. The use of high purity reference materials and stable isotope labelled internal standards ensure assay accuracies meeting the quality requirements of metrological reference measurement procedures. Key applications from the past and the present will be used to show how clinical relevant measurement services in endocrinology and therapeutic drug monitoring are made safe and reliable by the establishment of mass spectrometry based reference measurement procedures and services.

Plasma lipid levels are established risk factors for atherosclerotic cardiovascular disease (ASCVD) and interventions to lower plasma cholesterol were shown to reduce cardiovascular risk. The diagnosis of lipid metabolism disorders and cardiovascular risk assessment in patients relies on a standard lipid panel, consisting of plasma levels of total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. Given the significant residual cardiovascular risk, even in patients meeting their respective lipid treatment goals, there is an unmet need for additional biomarkers. Analysis of the concentrations of other lipid- and lipoprotein-related factors may offer the opportunity for a more comprehensive assessment of lipid metabolism and individual cardiovascular risk.