Drevland Ole Martin, Skadberg Eline, Tran Lan Anh, Åsberg Anders, Midtvedt Karsten, Robertsen Ida
Department of Pharmacy, University of Oslo, Oslo, Norway; and.
Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.
Ther Drug Monit. 2025 Apr 10. doi: 10.1097/FTD.0000000000001330.
Mycophenolic acid (MPA) is a cornerstone of immunosuppressive treatment in kidney transplant recipients (KTRs). Traditional therapeutic drug monitoring for MPA is based on venous blood sampling. Finger-prick capillary microsampling is patient-friendly and enables limited sampling to predict the area under the curve. A liquid chromatography-tandem mass spectrometry assay was used to detect MPA and its metabolite mycophenolic acid glucuronide (MPAG) using volumetric absorptive capillary microsampling (VAMS) was developed and clinically validated.
An assay based on VAMS and liquid chromatography-tandem mass spectrometry was validated bioanalytically and clinically. Agreement between dried microsamples and plasma samples was investigated in KTR on mycophenolate mofetil therapy. Paired microsamples and plasma samples were obtained before and at 0.5 and 2 hours postdosing. The samples were divided into development (75%) and validation (25%) datasets. Conversion from VAMS to plasma concentrations was established using a regression model, with at least 67% of paired samples required to fall within a mean relative difference of ±20%.
Twelve KTRs (median age: 49 years) provided 69 paired microsamples and plasma samples. For the VAMS method, the between-series mean accuracy was 90%-106% with a coefficient of variation <7% at concentrations of 0.25-32 mg/L (MPA) and 2.5-320 mg/L (MPAG). A conversion equation based on the regression model was applied and validated using an independent dataset. The mean relative differences between corrected microsamples and plasma samples were 1.9% for MPA and 2.7% for MPAG, with <5% outside ±20% for both analytes. Dried microsamples were stable for 3 months at ambient temperature.
The VAMS method demonstrated acceptable performance. MPA and MPAG can be reliably quantified using VAMS and are suitable for patient self-sampling in clinical pharmacokinetics studies of KTR.
霉酚酸（MPA）是肾移植受者（KTRs）免疫抑制治疗的基石。传统的MPA治疗药物监测基于静脉血采样。指尖毛细血管微量采样对患者友好，且能通过有限的采样来预测曲线下面积。已开发并在临床上验证了一种使用体积吸收性毛细血管微量采样（VAMS）的液相色谱 - 串联质谱分析法来检测MPA及其代谢物霉酚酸葡萄糖醛酸苷（MPAG）。
基于VAMS和液相色谱 - 串联质谱的分析方法在生物分析和临床方面得到了验证。在接受霉酚酸酯治疗的KTR中研究了干燥微量样本与血浆样本之间的一致性。在给药前以及给药后0.5小时和2小时获取配对的微量样本和血浆样本。样本被分为研发数据集（75%）和验证数据集（25%）。使用回归模型建立从VAMS到血浆浓度的转换关系，要求至少67%的配对样本的平均相对差异在±20%以内。
12名KTR（中位年龄：49岁）提供了69对微量样本和血浆样本。对于VAMS方法，在浓度为0.25 - 32 mg/L（MPA）和2.5 - 320 mg/L（MPAG）时，系列间平均准确度为90% - 106%，变异系数<7%。应用基于回归模型的转换方程并使用独立数据集进行验证。校正后的微量样本与血浆样本之间MPA的平均相对差异为1.9%，MPAG为2.7%，两种分析物均有<5%超出±20%。干燥的微量样本在室温下可稳定保存3个月。
VAMS方法表现出可接受的性能。MPA和MPAG可以使用VAMS可靠地定量，并且适用于KTR临床药代动力学研究中的患者自我采样。
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