Vikingsson Svante, Strömqvist Malin, Svedberg Anna, Hansson Johan, Höiom Veronica, Gréen Henrik
Clinical Pharmacology, Division of Drug Research, Department of Medical and Health Sciences, Linköping University, SE, 581 85, Linköping, Sweden.
Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, SE, 587 58, Linköping, Sweden.
Biomed Chromatogr. 2016 Aug;30(8):1234-9. doi: 10.1002/bmc.3672. Epub 2016 Jan 25.
A novel, rapid and sensitive liquid chromatography tandem-mass spectrometry method for quantification of vemurafenib in human plasma, that also for the first time allows for metabolite semi-quantification, was developed and validated to support clinical trials and therapeutic drug monitoring. Vemurafenib was analysed by precipitation with methanol followed by a 1.9 min isocratic liquid chromatography tandem masspectrometry analysis using an Acquity BEH C18 column with methanol and formic acid using isotope labelled internal standards. Analytes were detected in multireaction monitoring mode on a Xevo TQ. Semi-quantification of vemurafenib metabolites was performed using the same analytical system and sample preparation with gradient elution. The vemurafenib method was successfully validated in the range 0.5-100 μg/mL according to international guidelines. The metabolite method was partially validated owing to the lack of commercially available reference materials. For the first time concentration levels at steady state for melanoma patients treated with vemurafenib is presented. The low abundance of vemurafenib metabolites suggests that they lack clinical significance. Copyright © 2016 John Wiley & Sons, Ltd.
开发并验证了一种新颖、快速且灵敏的液相色谱串联质谱法，用于定量测定人血浆中的维莫非尼，该方法还首次实现了代谢物的半定量，以支持临床试验和治疗药物监测。采用甲醇沉淀法对维莫非尼进行分析，随后使用Acquity BEH C18柱，以甲醇和甲酸为流动相，采用同位素标记内标，进行1.9分钟的等度液相色谱串联质谱分析。在Xevo TQ上以多反应监测模式检测分析物。使用相同的分析系统和梯度洗脱的样品制备方法对维莫非尼代谢物进行半定量。根据国际指南，维莫非尼方法在0.5 - 100μg/mL范围内成功验证。由于缺乏市售参考物质，代谢物方法进行了部分验证。首次给出了接受维莫非尼治疗的黑色素瘤患者的稳态浓度水平。维莫非尼代谢物的低丰度表明它们缺乏临床意义。版权所有© 2016 John Wiley & Sons, Ltd.
