Ileana Constantinescu*, GABRIELA ISTRATE<br>Quantification of Cyclosporine, Tacrolimus and Sirolimus Concentrations from Whole Blood of Bone Marrow and Renal Transplantated Patients - Benefits for Long Term Outcome and Survival

Ileana Constantinescu*, GABRIELA ISTRATE
Quantification of Cyclosporine, Tacrolimus and Sirolimus Concentrations from Whole Blood of Bone Marrow and Renal Transplantated Patients - Benefits for Long Term Outcome and Survival

Abstract:

The aim of this study was to analyze the concentration of Cyclosporine (CSA), Tacrolimus and Sirolimus in whole blood after renal and bone marrow transplantations. Correlating these concentrations with clinical aspects, we could give more information about these immunosuppressive drugs that have narrow therapeutic indices as a result of highly variable inter-subject pharmacokinetics which require therapeutic drug monitoring to individualize dosage based on trough target concentration range. Measurements for quantification of any combination of these three major immunosuppressants in whole blood were performed on a system high performance liquid chromatography - HPLC (Perkin Elmer PE 200) -tandem mass spectrometer (3200API-AB Sciex) using a commercial kit from Chromsystems. For mass spectrometry, MS/MS, sample preparation has involved simple protein precipitation and solvent dissolution. Samples of transplant patients receiving cyclosporine, sirolimus and tacrolimus, were analyzed successively by LCMS/MS method using Solid Phase Extraction. Detection with mass spectrometry was afforded using multiple reaction monitoring (MRM) of the ammonium adducts of the immunosuppressive agents and their respective internal standards. The sensitivity, simplicity, universality and high throughput of the method make it suitable for clinical application in a transplant laboratory. Keywords: Cyclosporine, Tacrolimus, Sirolimus, kidney transplantation, bone marrow transplantation, whole blood, therapeutic drug monitoring, liquid chromatography-tandem mass spectrometry LCTMS, dosing

Issue: 2013, Volume 64, Issue 11

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