A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for monitoring drug exposure in hematopoietic stem cell transplant recipients

作者：Laverdiere Isabelle; Caron Patrick; Couture Felix; Levesque Eric^*; Guillemette Chantal

来源：Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2012, 885: 131-137.

DOI：10.1016/j.jchromb.2011.12.029

• Chromatography
• Mass spectrometry
• Calcineurin inhibitor
• Corticosteroid
• Methotrexate
• Mycophenolic acid

A liquid chromatography-tandem mass spectrometry method was developed for the quantification of circulating levels of multiple immunosuppressant drugs including cyclosporine (CsA), tacrolimus, methotrexate (Mtx), prednisone, prednisolone, methylprednisone, total and free mycophenolic acid (MPA), as well as MPA phenolic (MPAG) and acyl (AcMPAG) glucuronide metabolites. Linearity, precision and accuracy were validated within the typical therapeutic range of concentrations for each compound. The assay was linear over 0.125-25 ng/mL for tacrolimus, 1-500 ng/mL for prednisone/methylprednisone, 2-400 ng/mL for Mtx, 2-1000 ng/mL for prednisolone and from 7.5 to 1500ng/mL for CsA with the lowest limit of quantification (LLOQ) being 0.125, 1.00, 2.00, 2.00 and 7.5 ng/mL, respectively. The calibration curve concentrations for MPA and MPAG ranged from 50 to 50,000 ng/mL (LLOQ: 50ng/mL) and 10 to 10,000 ng/mL (LLOQ: 10ng/tnL) for AcMPAG. Mean recoveries in blood and plasma were 84% +/- 5.7%. The method could measure individual drugs with high sensitivity, accuracy (bias %26lt;= 14%), and reproducibility (CV %26lt;= 12.8%). Its clinical application was validated by measuring levels of these drugs in samples obtained from hematopoietic stem cell transplant recipients treated with combined immunosuppressive drug therapy. Our results indicate that this approach is suitable for simultaneous determination of in vivo levels of immunosuppressive drugs commonly used in combined therapies.

• 出版日期2012-2-15