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

被引:13
作者
Laverdiere, Isabelle [1 ,2 ]
Caron, Patrick [1 ,2 ]
Couture, Felix [3 ]
Levesque, Eric [1 ,3 ]
Guillemette, Chantal [1 ,2 ]
机构
[1] CHUQ, Res Ctr, Pharmacogen Lab, Quebec City, PQ G1V 4G2, Canada
[2] Univ Laval, Fac Pharm, Quebec City, PQ, Canada
[3] Univ Laval, Fac Med, Quebec City, PQ G1K 7P4, Canada
来源
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2012年 / 885卷
基金
加拿大健康研究院;
关键词
Chromatography; Mass spectrometry; Calcineurin inhibitor; Corticosteroid; Methotrexate; Mycophenolic acid; MYCOPHENOLIC-ACID GLUCURONIDE; HUMAN PLASMA; WHOLE-BLOOD; CYCLOSPORINE-A; HPLC-MS/MS; PERFORMANCE; TACROLIMUS; SIROLIMUS; MOFETIL; DEXAMETHASONE;
D O I
10.1016/j.jchromb.2011.12.029
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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 <= 14%), and reproducibility (CV <= 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. (C) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:131 / 137
页数:7
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