Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Georgstrasse 11, 32545 Bad Oeynhausen, Germany.
Talanta. 2010 Mar 15;80(5):1894-8. doi: 10.1016/j.talanta.2009.10.040. Epub 2009 Oct 24.
Mycophenolic acid (MPA) is an immunosuppressant drug which powerfully inhibits lymphocyte proliferation. Since the early 1990s it has been used to prevent rejection in organ transplantation. The requirement of therapeutic drug monitoring shown in previous studies raises the necessity of acquiring accurate and sensitive methods to measure MPA and its major metabolite mycophenolic acid glucuronide (MPAG). The authors developed a sample cleanup-free, rapid, and highly specific method for simultaneous measurement of MPA and MPAG in human plasma and serum using the novel technology of ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry. MPA- and MPAG-determinations were performed during a 2.0-min run time. Multiple calibration curves for the analysis of MPA and MPAG exhibited consistent linearity and reproducibility in the range of 0.05-100 (r>0.999) mg L(-1) and 4-4000 mg L(-1) (r>0.999), respectively. Limits of Detection were 0.014 mg L(-1) for MPA and 1.85 mg L(-1) for MPAG. Lower Limits of Quantification were 0.05 mg L(-1) for MPA and 2.30 mg L(-1) for MPAG. Interassay imprecision was <10% for both substances. Mean recovery was 103.6% (range 78.1-129.7%) for MPA and 111.1% (range 73.0-139.6%) for MPAG. Agreement was good for MPA and MPAG between the presented method and a validated HPLC-MS/MS method. The Passing-Bablok regression line for MPA and MPAG was HPLC-MS/MS=1.14 UPLC-MS/MS-0.14 [ mg L(-1)], r=0.96, and HPLC-MS/MS=0.77 UPLC-MS/MS+0.50 [ mg L(-1)], r=0.97, respectively. This sample cleanup-free and robust LC-MS/MS assay facilitates the rapid, accurate and simultaneous determination of MPA and MPAG in human body fluids.
霉酚酸（MPA）是一种强效抑制淋巴细胞增殖的免疫抑制剂。自 20 世纪 90 年代初以来，它一直被用于预防器官移植中的排斥反应。先前研究中显示的治疗药物监测需求提出了获得准确和敏感的方法来测量 MPA 和其主要代谢物霉酚酸葡萄糖醛酸（MPAG）的必要性。作者开发了一种无需样品净化、快速且高度特异的方法，用于使用超高效液相色谱-电喷雾串联质谱新技术同时测量人血浆和血清中的 MPA 和 MPAG。MPA 和 MPAG 的测定在 2.0 分钟的运行时间内完成。MPA 和 MPAG 分析的多校准曲线在 0.05-100（r>0.999）mg L（-1）和 4-4000 mg L（-1）（r>0.999）范围内表现出一致的线性和重现性。MPA 的检测限为 0.014 mg L（-1），MPAG 的检测限为 1.85 mg L（-1）。MPA 的定量下限为 0.05 mg L（-1），MPAG 的定量下限为 2.30 mg L（-1）。两种物质的批内精密度均<10%。MPA 的平均回收率为 103.6%（范围 78.1-129.7%），MPAG 的平均回收率为 111.1%（范围 73.0-139.6%）。所提出的方法与验证的 HPLC-MS/MS 方法之间，MPA 和 MPAG 的一致性良好。MPA 和 MPAG 的 Passing-Bablok 回归线分别为 HPLC-MS/MS=1.14 UPLC-MS/MS-0.14[mg L（-1）]，r=0.96 和 HPLC-MS/MS=0.77 UPLC-MS/MS+0.50[mg L（-1）]，r=0.97。这种无需样品净化且稳健的 LC-MS/MS 测定法有助于快速、准确和同时测定人体体液中的 MPA 和 MPAG。
