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

Principles and Applications of LC-MS/MS for the Quantitative Bioanalysis of Analytes in Various Biological Samples

“…The outcome of post-transplantation patient care has been improved dramatically over the last decades, primarily due to the availability of appropriate immunosuppressive regimens (Yang et al, 2005). The immunosuppressants present toxicity and have narrow therapeutic ranges.…”

“…For example, CsA showed numerous side effects including immunological, renal, hepatic and neurological complications, requiring dose adjustments or discontinuations in a significant percentage of patients (Rezzani, 2004). In addition, blood levels of the active drugs vary significantly in different individuals and ethnicities as well as different combinations of immunosuppressants (Holt, 2002;Yang et al, 2005). Therefore, the success of the post-transplant patient care largely depends on optimization of immunosuppressive therapy based on routine therapeutic drug monitoring (TDM).…”

“…Therefore, the success of the post-transplant patient care largely depends on optimization of immunosuppressive therapy based on routine therapeutic drug monitoring (TDM). The available analytical methods for monitoring immunosuppressant levels in patient specimens can be divided into two categories: immunoassays, such as microparticle enzyme immunoassay (MEIA), enzyme multiplied immunoassay technique (EMIT), fluorescent polarization immunoassay (FPIA), cloned enzyme donor immunoassay (CEDIA), and liquid chromatography-based methods (Yang et al, 2005). Immunoassays are widely employed to measure mycophenolic acid (MPA, active metabolite of MMF), CsA, tacrolimus, and sirolimus in human blood or serum/plasma.…”

“…Because of high specificity of MS/MS detection, the baseline separation of target compounds from their potential interferents by HPLC, which is a must for many HPLC-UV or HPLC-MS assays, becomes unnecessary leading to significant savings in analytical time, sample purification effort and chemical reagents. Usually a typical HPLC-MS/MS run can be accomplished within a few minutes in immunosuppressant monitoring (Yang et al, 2005;Ceglarek et al, 2006). In addition MS/MS can measure multiple ions or transitions to determine multiple drugs in a single analytical run.…”

“…There was no significant bias observed for dried blood sampling compared to venous blood sampling using 34 samples in 26 stable renal transplant outpatients measured by HPLC-MS/MS (Hoogtanders et al, 2007b). Because of various targets of action from different immunosuppressants, combinations of immunosuppressants are often used together to achieve synergistic therapeutic effects with reduced toxicity (Yang et al, 2005). Therefore, it is ideal to simultaneously measure these drugs in one analytical run.…”