Iboshi Hiromasa, Yamaguchi Hiroaki, Suzuki Hiroyuki, Kikuchi Masafumi, Tanaka Masaki, Takasaki Shinya, Takahashi Akiko, Maekawa Masamitsu, Shimada Miki, Matsuda Yasushi, Okada Yoshinori, Mano Nariyasu
*Laboratory of Clinical Pharmaceutical Science, Graduate School of Medicine, Tohoku University; †Department of Pharmaceutical Sciences, Tohoku University Hospital. Dr. Suzuki is now with the Department of Clinical Pharmaceutics, Tohoku Medical and Pharmaceutical University, Aoba-ku, Sendai, Japan. Dr. Shimada is now with the Division of Pharmacy, Tottori University Hospital, Yonago, Tottori, Japan; and ‡Department of Thoracic Surgery, Tohoku University Hospital, Aoba-ku, Sendai, Japan.
Ther Drug Monit. 2017 Dec;39(6):648-653. doi: 10.1097/FTD.0000000000000458.
Personalized immunosuppressive therapy, including accurate drug dosing based on the drug blood level, leads to better clinical outcomes, specifically regarding avoidance of drug-induced adverse effects and maintenance of efficacy. Mycophenolic acid (MPA) is used as an immunosuppressant in transplantation of various solid organs. The aim of this study was to develop a method for quantification of MPA and its metabolites, mycophenolic acid 7-O-glucuronide (MPAG) and mycophenolic acid acyl glucuronide, in dried blood spot (DBS) samples, using liquid chromatography/electrospray ionization/tandem mass spectrometry.
For sample preparation, a microwave-drying approach was used to deactivate enzymes and reduce drying time. Blood volume was calculated in a DBS disk of 3 mm diameter. Concentrations of analytes in plasma from patients receiving mycophenolate mofetil were compared with DBS samples after hematocrit correction.
The method yielded good recoveries of all 3 analytes (90.3%-104.2%). Blood volume in the disk was calculated as 3.0 ± 0.2 μL. Linearity over concentration ranges of 0.1-30 mcg/mL MPA, 0.1-200 mcg/mL MPAG, and 0.125-10 mcg/mL mycophenolic acid acyl glucuronide was obtained with r ≥0.999. Intraday and interday variations were less than 14.6%, and accuracy was within ±11.9%. Passing-Bablok analysis showed no significant differences between plasma concentrations and DBS concentrations after hematocrit correction of MPA and MPAG.
We developed and validated a liquid chromatography/electrospray ionization-tandem mass spectrometry method for analysis of MPA in DBS samples. The method is useful for monitoring the MPA blood level.
个性化免疫抑制治疗，包括基于药物血药浓度的精确给药，可带来更好的临床结果，特别是在避免药物引起的不良反应和维持疗效方面。霉酚酸（MPA）在各种实体器官移植中用作免疫抑制剂。本研究的目的是开发一种使用液相色谱/电喷雾电离/串联质谱法对干血斑（DBS）样本中的MPA及其代谢物霉酚酸7 - O - 葡萄糖醛酸苷（MPAG）和霉酚酸酰基葡萄糖醛酸苷进行定量的方法。
对于样本制备，采用微波干燥方法使酶失活并缩短干燥时间。计算直径为3 mm的DBS圆盘内的血量。对接受霉酚酸酯治疗的患者血浆中的分析物浓度与经血细胞比容校正后的DBS样本进行比较。
该方法对所有3种分析物的回收率良好（90.3% - 104.2%）。圆盘内的血量计算为3.0±0.2μL。在MPA浓度范围为0.1 - 30μg/mL、MPAG浓度范围为0.1 - 200μg/mL和霉酚酸酰基葡萄糖醛酸苷浓度范围为0.125 - 10μg/mL时获得线性，r≥0.999。日内和日间变化小于14.6%，准确度在±11.9%以内。通过 - 巴布洛赫分析表明，MPA和MPAG经血细胞比容校正后，血浆浓度与DBS浓度之间无显著差异。
我们开发并验证了一种用于分析DBS样本中MPA的液相色谱/电喷雾电离 - 串联质谱法。该方法可用于监测MPA血药浓度。
