Journal article
Quantification of the next-generation oral anti-tumor drugs dabrafenib, trametinib, vemurafenib, cobimetinib, pazopanib, regorafenib and two metabolites in human plasma by liquid chromatography-tandem mass spectrometry.
- Cardoso E School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
- Mercier T Laboratory of the Service of Clinical Pharmacology, Department of Laboratories, Lausanne University Hospital, Lausanne, Switzerland.
- Wagner AD Service of Medical Oncology, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
- Homicsko K Service of Medical Oncology, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
- Michielin O Service of Medical Oncology, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
- Ellefsen-Lavoie K Center of Experimental Therapeutics, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
- Cagnon L Center of Experimental Therapeutics, Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland.
- Diezi M Paediatric Hemato-Oncology Unit, Department of Paediatrics, Lausanne University Hospital, Lausanne, Switzerland.
- Buclin T Service of Clinical Pharmacology, Department of Laboratories, Lausanne University Hospital, Lausanne, Switzerland.
- Widmer N Service of Clinical Pharmacology, Department of Laboratories, Lausanne University Hospital, Lausanne, Switzerland; Pharmacy of Eastern Vaud Hospitals, Vevey, Switzerland.
- Csajka C School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland; Service of Clinical Pharmacology, Department of Laboratories, Lausanne University Hospital, Lausanne, Switzerland.
- Decosterd L Laboratory of the Service of Clinical Pharmacology, Department of Laboratories, Lausanne University Hospital, Lausanne, Switzerland. Electronic address: LaurentArthur.Decosterd@chuv.ch.
- 2018-03-16
Published in:
- Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. - 2018
Drug monitoring
LC-MS/MS
Targeted anticancer therapy
Tyrosine kinase inhibitor
Administration, Oral
Antineoplastic Agents
Azetidines
Child
Chromatography, High Pressure Liquid
Humans
Imidazoles
Indoles
Limit of Detection
Linear Models
Oximes
Phenylurea Compounds
Piperidines
Pyridines
Pyridones
Pyrimidines
Pyrimidinones
Reproducibility of Results
Sulfonamides
Tandem Mass Spectrometry
Vemurafenib
English
A sensitive and selective method of high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS) has been developed for the simultaneous quantification of six anticancer protein kinase inhibitors (PKIs), dabrafenib, trametinib, vemurafenib, cobimetinib, pazopanib, regorafenib, and two active metabolites (regorafenib-M2 and regorafenib-M5) in human plasma. Plasma protein precipitation with methanol enables the sample extraction of 100 μL aliquot of plasma. Analytes are detected by electrospray triple-stage quadrupole mass spectrometry and quantified using the calibration curves with stable isotope-labeled internal standards. The method was validated based on FDA recommendations, including assessment of extraction yield (74-104%), matrix effects, analytical recovery (94-104%) with low variability (<15%). The method is sensitive (lower limits of quantification within 1 to 200 ng/mL), accurate (intra- and inter-assay bias: -0.3% to +12.7%, and -3.2% to +6.3%, respectively) and precise (intra- and inter-assay CVs within 0.7-7.3% and 2.5-8.0%, respectively) over the clinically relevant concentration range (upper limits of quantification 500 to 100,000 ng/mL). This method is applied in our laboratory for both clinical research programs and routine therapeutic drug monitoring service of PKIs.
- Language
-
- English
- Open access status
- closed
- Identifiers
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- DOI 10.1016/j.jchromb.2018.02.008
- PMID 29544202
- Persistent URL
- https://sonar.ch/global/documents/46529
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