化学
类风湿性关节炎
色谱法
蛋白质沉淀
治疗药物监测
分析物
串联质谱法
药理学
质谱法
药代动力学
内科学
医学
作者
Jens Martens‐Lobenhoffer,Stylianos Tomaras,Eugen Feist,Stefanie M. Bode‐Böger
标识
DOI:10.1016/j.jchromb.2021.123076
摘要
Upadacitinib is a selective janus-kinase-1 inhibitor effective in the treatment of autoimmune related diseases like rheumatoid arthritis or psoriatic arthritis. Here, we described a LC-MS/MS method for the quantification of upadacitinib in human plasma applicable for therapeutic drug monitoring. Pexidartinib was used as internal standard. Plasma samples were prepared by acidic protein precipitation and the analytes were separated on a C-18 reversed phase column. Detection took place by tandem mass spectroscopy after ionization in the positive mode and collision induced fragmentation at m/z 381 → 256, 213 for upadacitinib and m/z 418 → 258, 165 for pexidartinib. The calibration function was linear in the range of 0.15 - 150 ng/mL. Precisions and accuracies were better than 10% in intra- as well as inter-day evaluations. The method was applied in therapeutic drug monitoring of patients undergoing treatment for rheumatoid arthritis with the standard dose of 15 mg upadacitinib extended release formulation once daily. At steady state, we found trough levels of 4.13 (3.51 - 11.0) ng/mL, which is comparable to values found in healthy volunteers receiving the same dose (2.8 ± 1.2 ng/mL).
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