Study On Clinical Monitoring Methods For Immunosuppressants Used In Organ Transplantation

Transplant recipients are treated lifelong with immunosuppressants to avoid organ rejection. Most commonly used immunosuppressants are cyclosporin A (CsA) and tacrolimus(FK506). However, all immunosuppressants have to be used within a narrow therapeutic window. Therefore, it is most important to regularly control drug level concentrations in blood by therapeutic drug monitoring. Nowadays immunoassay and the high performance liquid chromatography (HPLC) are preferably applied for the determination of immunosuppressants. Here the analysis methods and assessment of these two immunosuppressants are investigated.To develop HPLC in combination with atmospheric pressure ionization mass spectrometry method for determination of CsA and its main metabolites in whole blood samples.To develop micellar electrokinetic chromatography (MEKC) method for determination of CsA in whole blood samples.To evaluate MEKC, LC-MS and mFPIA, all the blood samples determinated by the methods were compared, and the impacts on concentratins of CsA and its main metabolites were analyzed using multiple linear regression and canonical correlation analysis. As a result, we concluded that when hepatoxicity and nephrotoxicity occurred, FPIA often produce erroneous results, as a result of cross-reactivity with metabolites of the parent drug. Chromatographies are advocated as a highly selective method for the analysis of immunosuppressants.