Liquid chromatography/mass spectrometry for therapeutic drug monitoring of immunosuppressants

Abstract

The benefit of therapeutic drug monitoring (TDM) of immunosuppressants like sirolimus, everolimus, tacrolimus, and cyclosporine for the clinical outcome of transplant recipients has been shown in numerous studies. For the monitoring of cyclosporine, tacrolimus and mycophenolic acid immunoassays are mostly used. However, these have the disadvantage that on one hand the antibodies used cross-react to a varying extent with metabolites and on the other hand different immunosuppressants cannot be measured simultaneously. No commercial immunoassays are available for the quantification of sirolimus and everolimus. In modern immunosuppressive regimens, two or even more different immunosuppressants are combined, which allows a dose reduction of each single component. Analytical laboratories will consequently be challenged with blood samples containing a variety of different immunosuppressants in very low concentrations. Therefore, the high sensitive and specific detection techniques like liquid chromatography/liquid chromatography–mass spectrometry (LC–LC/MS), liquid chromatography/mass spectrometry (LC/MS) and LC/MS–MS seem to be the methods of choice now and in near future. However, the user of these new applications have to be aware of some pitfalls, as well.