Bihan Kevin, Sauzay Chloé, Goldwirt Lauriane, Charbonnier-Beaupel Fanny, Hulot Jean-Sebastien, Funck-Brentano Christian, Zahr Noël
Departments of *Pharmacology and CIC-1421, and †Pharmacy, Pitié-Salpêtrière Hospital, AP-HP; ‡Department of Pharmacology and UMR ICAN 1166, Faculty of Medicine, Sorbonne University, UPMC Univ Paris 06; and §INSERM, CIC-1421, and UMR ICAN 1166, Paris, France.
Ther Drug Monit. 2015 Feb;37(1):132-6. doi: 10.1097/FTD.0000000000000110.
Vemurafenib (Zelboraf) is a new tyrosine kinase inhibitor that selectively targets activated BRAF V600E gene and is indicated for the treatment of advanced BRAF mutation-positive melanoma. We developed a simple method for vemurafenib quantification using liquid chromatography-tandem mass spectrometry. A stability study of vemurafenib in human plasma was also performed.
(13)C(6)-vemurafenib was used as the internal standard. A single-step protein precipitation was used for plasma sample preparation. Chromatography was performed on an Acquity UPLC system (Waters) with chromatographic separation by the use of an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7-mm particle size; Waters). Quantification was performed using the monitoring of multiple reactions of following transitions: m/z 488.2 → 381.0 for vemurafenib and m/z 494.2 → 387.0 for internal standard.
This method was linear over the range from 1.0 to 100.0 mcg/mL. The lower limit of quantification was 0.1 mcg/mL for vemurafenib in plasma. Vemurafenib remained stable for 1 month at all levels tested, when stored indifferently at room temperature (20 °C), at +4 °C, or at -20 °C. This method was used successfully to perform a plasma pharmacokinetic study of vemurafenib in a patient after oral administration at a steady state.
This liquid chromatography-tandem mass spectrometry method for vemurafenib quantification in human plasma is simple, rapid, specific, sensitive, accurate, precise, and reliable.
维莫非尼（佐博伏）是一种新型酪氨酸激酶抑制剂，可选择性靶向激活的BRAF V600E基因，用于治疗晚期BRAF突变阳性黑色素瘤。我们开发了一种使用液相色谱 - 串联质谱法定量维莫非尼的简单方法。还进行了维莫非尼在人血浆中的稳定性研究。
使用（13）C（6）-维莫非尼作为内标。采用单步蛋白沉淀法制备血浆样品。在Acquity UPLC系统（沃特世公司）上进行色谱分析，使用Acquity UPLC BEH C18柱（2.1×50 mm，1.7μm粒径；沃特世公司）进行色谱分离。通过监测以下跃迁的多反应进行定量：维莫非尼的m/z 488.2→381.0，内标的m/z 494.2→387.0。
该方法在1.0至100.0 mcg/mL范围内呈线性。血浆中维莫非尼的定量下限为0.1 mcg/mL。维莫非尼在所有测试水平下，于室温（20°C）、+4°C或-20°C下随意储存时，均可稳定保存1个月。该方法成功用于在一名患者口服维莫非尼达到稳态后进行血浆药代动力学研究。
这种用于人血浆中维莫非尼定量的液相色谱 - 串联质谱法简单、快速、特异、灵敏、准确、精密且可靠。
