Liquid chromatography-tandem mass spectrometric assay for the multikinase inhibitor regorafenib in plasma.
Liquid chromatography-tandem mass spectrometric assay for the multikinase inhibitor regorafenib in plasma.
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血浆中多激酶抑制剂瑞戈非尼的液相色谱-串联质谱测定。
DOI：
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
R. Sparidans
中科院分区：
文献类型：
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作者：
D. Luethi;S. Durmuş;A. Schinkel;J. Schellens;J. Beijnen;R. Sparidans
瑞戈非尼最近被批准用于治疗结直肠癌。开发了一种用于这种多激酶抑制剂的生物分析液相色谱-串联质谱测定法，并在血浆中进行了验证。测定的浓度范围为25- 25，000 ng/mL。采用乙腈沉淀蛋白质作为样品前处理，索拉非尼作为内标。用甲醇（25%，v/v）稀释浸提液，然后进样至亚2 μm颗粒、桥连乙基硅杂合三官能键合C18色谱柱上。使用在甲醇-水混合物中的0.02%（v/v）甲酸进行等度洗脱。在正电喷雾电离后，通过三重四极杆质谱仪以所选择的反应监测模式监测化合物。采用双对数校准;日内精密度、日间精密度和准确度分别为3.2- 9.2%、4.1- 12.3%和94.8- 103.0%。在所有相关储存条件下观察到高药物稳定性。在野生型FVB小鼠的药代动力学研究中，该测定法用于测量药物浓度。
Regorafenib has recently been approved for the treatment of colorectal cancer. A bioanalytical liquid chromatography-tandem mass spectrometric assay for this multikinase inhibitor was developed and validated in plasma. The concentration range of the assay was 25-25,000 ng/mL. Protein precipitation with acetonitrile was used as sample pre-treatment with sorafenib as internal standard. The extract was diluted with methanol (25%, v/v) and then injected onto the sub-2 µm particle, bridged ethylsilicia hybrid trifunctional bonded C18 column. Isocratic elution using 0.02% (v/v) formic acid in a methanol-water mixture was used. Compounds were monitored by a triple quadrupole mass spectrometer in the selected reaction monitoring mode after positive electrospray ionization. Double logarithmic calibration was used; within-day precisions, between-day precisions, and accuracies were 3.2-9.2, 4.1-12.3 and 94.8-103.0%, respectively. High drug stability was observed under all relevant storage conditions. The assay was used to measure drug concentrations in a pharmacokinetic study in wild-type FVB mice.