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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
Author(s) -
Liu Yan,
Liu Longshan,
Li Jingjie,
Fu Qian,
Zhang Huanxi,
Wu Chenglin,
Li Jun,
Zhong Guoping,
Zheng Yifan,
Chen Xiao,
Wang Changxi,
Chen Pan
Publication year - 2021
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4989
Subject(s) - chemistry , chromatography , free fraction , formic acid , pharmacokinetics , triple quadrupole mass spectrometer , mycophenolic acid , electrospray ionization , selected reaction monitoring , therapeutic drug monitoring , mass spectrometry , transplantation , pharmacology , tandem mass spectrometry , surgery , medicine , biochemistry , plasma protein binding
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 C 18 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.