Benoit-Biancamano Marie-Odile, Caron Patrick, Lévesque Eric, Delage Robert, Couture Félix, Guillemette Chantal
Canada Research Chair in Pharmacogenomics, Laboratory of Pharmacogenomics, Oncology and Molecular Endocrinology Research Center, CHUL Research Center and Faculty of Pharmacy, Laval University, G1V 4G2 Québec, Canada.
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Oct 15;858(1-2):159-67. doi: 10.1016/j.jchromb.2007.08.023. Epub 2007 Aug 24.
A method to determine total and free mycophenolic acid (MPA) and its metabolites, the phenolic (MPAG) and acyl (AcMPAG) glucuronides, using HPLC and mass spectrometry was developed. Mean recoveries in plasma and urine samples were >85%, and the lower limits of quantification for MPA, MPAG and AcMPAG were 0.05, 0.05 and 0.01 mg/L, respectively. For plasma, the assay was linear over 0.05-50 mg/L for MPA and MPAG, and from 0.01 to 10mg/L for AcMPAG. A validation study demonstrated good inter- and intra-day precision (CV<or=11%) and accuracy (bias<or=16%) and satisfactory specificity and stability. Pharmacokinetic parameters were assessed in plasma and urine from healthy volunteers after an oral dose of mycophenolate mofetil.
开发了一种使用高效液相色谱法（HPLC）和质谱法测定总霉酚酸（MPA）、游离霉酚酸及其代谢物酚性葡糖醛酸化物（MPAG）和酰基葡糖醛酸化物（AcMPAG）的方法。血浆和尿液样本中的平均回收率>85%，MPA、MPAG和AcMPAG的定量下限分别为0.05、0.05和0.01mg/L。对于血浆，MPA和MPAG在0.05 - 50mg/L范围内呈线性，AcMPAG在0.01至10mg/L范围内呈线性。一项验证研究表明，该方法具有良好的日间和日内精密度（CV≤11%）和准确度（偏差≤16%），以及令人满意的特异性和稳定性。在健康志愿者口服霉酚酸酯后，对其血浆和尿液中的药代动力学参数进行了评估。
