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Simple and cost-effective liquid chromatography-mass spectrometry method to measure dabrafenib quantitatively and six metabolites semi-quantitatively in human plasma
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.
Karolinska University Hospital Solna, Sweden.
Karolinska University Hospital Solna, Sweden.
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2017 (English)In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 409, no 15, 3749-3756 p.Article in journal (Refereed) Published
Abstract [en]

Dabrafenib is an inhibitor of BRAF V600E used for treating metastatic melanoma but a majority of patients experience adverse effects. Methods to measure the levels of dabrafenib and major metabolites during treatment are needed to allow development of individualized dosing strategies to reduce the burden of such adverse events. In this study, an LC-MS/MS method capable of measuring dabrafenib quantitatively and six metabolites semi-quantitatively is presented. The method is fully validated with regard to dabrafenib in human plasma in the range 5-5000 ng/mL. The analytes were separated on a C18 column after protein precipitation and detected in positive electrospray ionization mode using a Xevo TQ triple quadrupole mass spectrometer. As no commercial reference standards are available, the calibration curve of dabrafenib was used for semi-quantification of dabrafenib metabolites. Compared to earlier methods the presented method represents a simpler and more cost-effective approach suitable for clinical studies.

Place, publisher, year, edition, pages
SPRINGER HEIDELBERG , 2017. Vol. 409, no 15, 3749-3756 p.
Keyword [en]
Bioanalytical methods; Biological samples; Drug monitoring/drug screening; HPLC; Mass spectrometry/ICP-MS
National Category
Biomedical Laboratory Science/Technology
Identifiers
URN: urn:nbn:se:liu:diva-138223DOI: 10.1007/s00216-017-0316-8ISI: 000401407900006PubMedID: 28429064OAI: oai:DiVA.org:liu-138223DiVA: diva2:1109401
Note

Funding Agencies|Swedish Research Council; Swedish Cancer Society; County Council of Ostergotland; County Council of Stockholm-Gotland; Medical Research Council of Southeast Sweden; Swedish Medical Research Council; Cancer Research Foundations of Radiumhemmet; Karolinska Institutet

Available from: 2017-06-14 Created: 2017-06-14 Last updated: 2017-07-03

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Vikingsson, SvanteDahlberg, Jan-OlofGreen, Henrik
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CiteExportLink to record
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Citation style
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