Immunosuppressants: Pharmacokinetics, methods of monitoring and role of high performance liquid chromatography/mass spectrometry

Immunosuppressants are used in posttransplantation patient care and autoimmune disease therapy. Because of their narrow therapeutic ranges and high variations of the interindividual pharmacokinetics, therapeutic drug monitoring (TDM) of immunosuppressants is critical. The most common methods used in the clinical laboratories for measurement of immunosuppressants are immunoassays and liquid chromatography coupled with ultraviolet detection, which are subject to interference by the metabolites formed in vivo. Liquid chromatography coupled with mass spectrometry (LC/MS) is a powerful analytical tool that provides high specificity and sensitivity in TDM of the immunosuppressants. In this article, the recent development of LC/MS application in measurement of the immunosuppressants is reviewed, and its benefits and pitfalls are critically discussed. The immunosuppressants included in this review are cyclosporine A, tacrolimus, sirolimus, everolimus, and mycophenolic acid. Because of the simplified sample preparation and the high sensitivity and specificity, LC/MS has shown great potential to be the method of choice for TDM of the immunosuppressants, especially for simultaneous multiple-drug monitoring.