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Validated LC–MS/MS method for quantitation of total and free mycophenolic acid concentration and its application to a pharmacokinetic study in pediatric renal transplant recipients
Biomedical Chromatography ( IF 1.8 ) Pub Date : 2020-09-22 , DOI: 10.1002/bmc.4989
Yan Liu 1, 2 , Longshan Liu 3 , Jingjie Li 4 , Qian Fu 3 , Huanxi Zhang 3 , Chenglin Wu 3 , Jun Li 3 , Guoping Zhong 5 , Yifan Zheng 1 , Xiao Chen 1 , Changxi Wang 3, 6 , Pan Chen 1
Affiliation  

A simple and sensitive LC–MS/MS method was established to quantify total and free mycophenolic acid (MPA) plasma concentrations during immunosuppressive medication for pediatric renal transplantation. The chromatographic separation was performed with the Hypersil GOLD C18 column, using a mobile phase consisting of 0.1% formic acid in water and acetonitrile (60:40, v/v) at an isocratic flow rate of 0.4 ml/min. An Agilent 6420 triple quadrupole mass spectrometer was operated via a positive electrospray ionization interface using the transitions m/z 321.14 → 206.9 for MPA and m/z 324.15 → 209.9 for MPA‐d3 (internal standard). The linearity was 0.1–50 μg/ml for total MPA and 0.0025–0.5 μg/ml for free MPA. The within‐run and between‐run precisions were all <5% and accuracy was within 96.23–107.63%. The validated method was successfully aspplied to a pharmacokinetic study in 28 pediatric renal recipients. The mean free fraction of MPA in our patients was 0.89% (ranging from 0.62 to 1.25%) and albumin level played a major role in the variability of free fraction of MPA, thus, in pediatric patients with hypoproteinemia, close free drug monitoring and dose adjustments should be considered to prevent toxicity.

中文翻译:

经验证的LC-MS / MS方法用于定量总麦考酚酚酸和游离麦考酚酸的浓度,并将其应用于小儿肾移植受者的药代动力学研究

建立了一种简单而灵敏的LC-MS / MS方法,以量化用于儿科肾移植的免疫抑制药物治疗期间总和游离的麦考酚酸(MPA)血浆浓度。用Hypersil GOLD C 18色谱柱进行色谱分离,所用流动相由0.1%的甲酸水溶液和乙腈(60:40,v / v)组成,等度流速为0.4 ml / min。安捷伦6420三重四极杆质谱仪通过正电喷雾电离界面使用m / z 321.14→206.9的MPA和m / z跃迁进行操作对于MPA-d3(内部标准)为324.15→209.9。总MPA的线性为0.1–50μg/ ml,游离MPA的线性为0.0025–0.5μg/ ml。批内和批间精度均<5%,准确度在96.23–107.63%之内。经验证的方法已成功应用于28位儿科肾脏接受者的药代动力学研究。我们患者中MPA的平均游离分数为0.89%(介于0.62至1.25%之间),白蛋白水平在MPA游离分数的变异性中起着主要作用,因此,在低蛋白血症的小儿患者中,密切监测游离药物并剂量应考虑调整以防止毒性。
更新日期:2020-09-22
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