Heinig Katja, Bucheli Franz, Hartenbach Roswitha, Gajate-Perez Almudena
F. Hoffmann-La Roche Ltd, Pharma Research, Nonclinical Safety, Bioanalytical Section, CH-4070 Basel, Switzerland.
Bioanalysis. 2010 Aug;2(8):1423-35. doi: 10.4155/bio.10.99.
Analysis of mycophenolic acid (MPA), the active form of the immunosuppressive drug mycophenolate mofetil, and its glucuronide metabolite MPAG is required for therapeutic monitoring and postmarketing clinical studies. Dried blood spots (DBS) and dried plasma spots (DPS) could be alternatives to conventional assays for small-volume sampling and easy shipment.
A LC-MS/MS method with online SPE was established using stable isotope labeled analytes as internal standards. The quantitation limits were set at 0.1 and 1 µg/ml, for total MPA and MPAG, respectively, in plasma, blood, DBS and DPS, but 100-fold lower for free MPA in ultrafiltrate. Ahlstrom 226 or Whatman FTA(®) DMPK-B cards were well suited for DBS and DPS analyses.
MPA and MPAG were analyzed in human plasma and blood either as liquid or dried on cards with similar assay quality. Care should be taken to avoid back-conversion of an instable acyl glucuronide metabolite to MPA.
免疫抑制药物霉酚酸酯的活性形式霉酚酸（MPA）及其葡糖醛酸代谢物MPAG的分析对于治疗监测和上市后临床研究是必要的。干血斑（DBS）和干血浆斑（DPS）可作为传统检测方法的替代方法，用于小体积采样和便捷运输。
建立了一种采用在线固相萃取的液相色谱-串联质谱法，使用稳定同位素标记的分析物作为内标。血浆、血液、DBS和DPS中总MPA和MPAG的定量限分别设定为0.1和1 μg/ml，但超滤液中游离MPA的定量限低100倍。Ahlstrom 226或Whatman FTA(®) DMPK-B卡非常适合DBS和DPS分析。
MPA和MPAG在人血浆和血液中作为液体或干片进行分析，检测质量相似。应注意避免不稳定的酰基葡糖醛酸代谢物逆转为MPA。
