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Simultaneous Quantification of Mycophenolic Acid and Its Glucuronide Metabolite in PBMCs from Kidney Transplant Recipients by LC-MS/MS 期刊论文

编号：

BC0931E6A21A9F4626FF434E4804B094
作者：

Yang, Na(杨娜)#^[1,2]Zhao, Yuqing#^[3]Liu, Shiyu^[1];Zhou, Yifan^[1,2];Ji, Xinyue^[1];Zhang, Tianqi(张天祺)^[1,2]Sun, Runbin^[4];Zhu, Huaijun(朱怀军)^[1,2]Du, Yao(杜瑶)*^[1,2]Wang, Min(王敏)*^[1,2]
语种：

英文
期刊：

DRUG DESIGN DEVELOPMENT AND THERAPY ISSN：1177-8881 2026 年 20 卷
收录：
关键词：

mycophenolic acid mycophenolic acid glucuronide LC-MS/MS therapeutic drug monitoring mycophenolate mofetil enteric-coated mycophenolate sodium
摘要：

Background: Mycophenolic acid (MPA), administered as mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS), is the first-line immunosuppressant for kidney transplant patients. Traditional plasma-based therapeutic drug monitoring (TDM) for MPA fails to accurately reflect intracellular drug exposure at the pharmacological action site.
Purpose: This study aimed to establish and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of MPA and its glucuronide metabolite, MPAG, in peripheral blood mononuclear cells (PBMCs) to support cellular pharmacokinetic (PK) assessment.
Methods: Chromatographic separation was performed on a BEH C18 column using methanol-water containing 0.1% formic acid and 5 mmol/L ammonium acetate. A total of 139 PBMC samples from 40 kidney transplant recipients (n=19 receiving EC-MPS; n=21 receiving MMF) were analyzed to evaluate the plasma-PBMC PK correlations and gender-related differences.
Results: The method exhibited excellent linearity over the concentration range of 0.2- 500 ng/mL (R-2 > 0.998), along with acceptable precision, accuracy and matrix effect. The analytes remained stable under various experimental conditions. Significant inter-individual variability in intracellular MPA and MPAG concentrations was observed among patients. Spearman correlation analysis demonstrated a weak-to-moderate positive correlation between plasma and intracellular PBMC concentrations of MPA (EC-MPS, R-s=0.396; MMF, R-s=0.480). Additionally, the concentration-time profiles of MPA and MPAG in PBMCs of kidney transplant recipients after administration of EC-MPS or MMF exhibited different characteristics. No significant gender-based differences in plasma and PBMCs were observed.
Conclusion: We established and validated an LC-MS/MS method for simultaneous quantification of intracellular MPA and MPAG. The observed weak-to-moderate correlation between plasma and PBMC exposure highlights the inherent limitations of conventional plasma-based TDM for MPA. Collectively, our study provides a feasible approach for monitoring intracellular drug levels and facilitates the optimization of individualized immunosuppressive dosing regimens for renal transplant recipients.
推荐引用方式
GB/T 7714：

Yang Na,Zhao Yuqing,Liu Shiyu, et al. Simultaneous Quantification of Mycophenolic Acid and Its Glucuronide Metabolite in PBMCs from Kidney Transplant Recipients by LC-MS/MS [J].DRUG DESIGN DEVELOPMENT AND THERAPY,2026,20.
APA：

Yang Na,Zhao Yuqing,Liu Shiyu,Zhou Yifan,&Wang Min.(2026).Simultaneous Quantification of Mycophenolic Acid and Its Glucuronide Metabolite in PBMCs from Kidney Transplant Recipients by LC-MS/MS .DRUG DESIGN DEVELOPMENT AND THERAPY,20.
MLA：

Yang Na, et al. "Simultaneous Quantification of Mycophenolic Acid and Its Glucuronide Metabolite in PBMCs from Kidney Transplant Recipients by LC-MS/MS" .DRUG DESIGN DEVELOPMENT AND THERAPY 20(2026).
入库时间：

8/12/2026 9:23:22 PM
更新时间：

8/13/2026 12:00:03 AM

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