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Novel rapid liquid chromatography tandem masspectrometry method for vemurafenib and metabolites in human plasma, including metabolite concentrations at steady-state.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
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2016 (English)In: BMC Biomedical chromotography, ISSN 0269-3879, E-ISSN 1099-0801, Vol. 30, no 8, 1234-1239 p.Article in journal (Refereed) Published
Abstract [en]

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 multi reaction 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 due 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. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
John Wiley & Sons, 2016. Vol. 30, no 8, 1234-1239 p.
Keyword [en]
BRAFV600E; LC-MS/MS; melanoma; metabolites;validation
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-126098DOI: 10.1002/bmc.3672ISI: 000379971200010PubMedID: 26683023OAI: oai:DiVA.org:liu-126098DiVA: diva2:911793
Note

Funding agencies: Swedish Research Council [C0592901, A0671101]; Swedish Cancer Society [130335]; County Council of Ostergotland; County Council of Stockholm-Gotland; Medical Research Council of Southeast Sweden [388611]; Swedish Medical Research Council; Radiumhemmet Rese

Available from: 2016-03-14 Created: 2016-03-14 Last updated: 2016-08-22Bibliographically approved

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Vikingsson, SvanteStrömqvist, MalinSvedberg, AnnaGréen, Henrik
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