Therapeutic drug monitoring of immunosuppressants by liquid chromatography-mass spectrometry

Immunosuppressant medications allow the transplantation of tens of thousands of allografts per year and consequently have great potential to decrease patient morbidity and mortality. However, some medications have great risk associated with over- and under-dosing leading to adverse effects or allograft rejection, respectively. This necessitates immunosuppressant therapeutic drug monitoring accomplished by immunoassay or liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The former's accuracy can be hindered by metabolites of immunosuppressant medications, antibodies against these medications and heterophilic antibodies. Although LC-MS/MS has superior specificity which allows it to be less susceptible to interference, this methodology lacks standardization and the necessary throughput. Recent developments in LC-MS/MS quantitation, however, include patient-friendly sample submission as dried blood spots, higher sample throughput and commercialization. Here we critically review recent LC-MS/MS publications (January 2010 to July 2015) on the quantitation of cyclosporine A, tacrolimus, sirolimus and everolimus.