Merrigan Stephen D, Kish-Trier Erik, Seegmiller Jesse C, Johnson-Davis Kamisha L
ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, United States.
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States.
Clin Mass Spectrom. 2017 Jul 10;3:41-48. doi: 10.1016/j.clinms.2017.07.001. eCollection 2017 Jan.
Mycophenolic acid (MPA) is the active metabolite of the immunosuppressant drug mycophenolate mofetil (MMF), which is commonly prescribed after organ transplantation in conjunction with other immunosuppressants. MMF therapy is monitored to balance therapeutic efficacy with minimizing adverse effects associated with high serum concentrations. A LC-MS/MS method was developed for the quantification of MPA and two additional metabolites, 7-O-mycophenolic acid glucuronide (MPAG) and mycophenolic acid acyl-glucuronide (AcMPAG), in serum using reverse-phase chromatography and multiple reaction monitoring (MRM) in positive electrospray ionization mode. Analytes were chromatographically resolved and the method was linear from 0.5 to 30.0 µg/ml MPA, 4.7 to 300 µg/ml MPAG, and from 0.5 to 30.0 µg/ml AcMPAG. Calibration curves for all analytes had r ≥ 0.990. Intra- and inter-assay imprecision coefficients of variation (CVs) were ≤6.9% and ≤14.5%, respectively. No ion suppression or interferences were observed. The method compared favorably with an unaffiliated reference laboratory. Retrospective data analyses indicate interpatient differences in drug metabolism.
霉酚酸（MPA）是免疫抑制剂霉酚酸酯（MMF）的活性代谢产物，MMF常用于器官移植后与其他免疫抑制剂联合使用。对MMF治疗进行监测，以平衡治疗效果并将与高血清浓度相关的不良反应降至最低。建立了一种液相色谱-串联质谱（LC-MS/MS）方法，用于定量血清中的MPA以及另外两种代谢产物，7-O-霉酚酸葡萄糖醛酸苷（MPAG）和霉酚酸酰基葡萄糖醛酸苷（AcMPAG），采用反相色谱法和正电喷雾电离模式下的多反应监测（MRM）。分析物通过色谱法分离，该方法在MPA浓度为0.5至30.0μg/ml、MPAG浓度为4.7至300μg/ml以及AcMPAG浓度为0.5至30.0μg/ml范围内呈线性。所有分析物的校准曲线r≥0.990。批内和批间精密度变异系数（CVs）分别≤6.9%和≤14.5%。未观察到离子抑制或干扰。该方法与一家独立的参考实验室相比具有优势。回顾性数据分析表明患者之间存在药物代谢差异。
