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.

Détails

ID Serval
serval:BIB_E8B0234B5672
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
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.
Périodique
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
Auteur(s)
Cardoso E., Mercier T., Wagner A.D., Homicsko K., Michielin O., Ellefsen-Lavoie K., Cagnon L., Diezi M., Buclin T., Widmer N., Csajka C., Decosterd L.
ISSN
1873-376X (Electronic)
ISSN-L
1570-0232
Statut éditorial
Publié
Date de publication
15/04/2018
Peer-reviewed
Oui
Volume
1083
Pages
124-136
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
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.
Mots-clé
Administration, Oral, Antineoplastic Agents/administration & dosage, Antineoplastic Agents/blood, Antineoplastic Agents/chemistry, Antineoplastic Agents/pharmacokinetics, Azetidines/administration & dosage, Azetidines/blood, Azetidines/chemistry, Azetidines/pharmacokinetics, Child, Chromatography, High Pressure Liquid/methods, Humans, Imidazoles/administration & dosage, Imidazoles/blood, Imidazoles/chemistry, Imidazoles/pharmacokinetics, Indoles/administration & dosage, Indoles/blood, Indoles/chemistry, Indoles/pharmacokinetics, Limit of Detection, Linear Models, Oximes/administration & dosage, Oximes/blood, Oximes/chemistry, Oximes/pharmacokinetics, Phenylurea Compounds/administration & dosage, Phenylurea Compounds/blood, Phenylurea Compounds/chemistry, Phenylurea Compounds/pharmacokinetics, Piperidines/administration & dosage, Piperidines/blood, Piperidines/chemistry, Piperidines/pharmacokinetics, Pyridines/administration & dosage, Pyridines/blood, Pyridines/chemistry, Pyridines/pharmacokinetics, Pyridones/administration & dosage, Pyridones/blood, Pyridones/chemistry, Pyridones/pharmacokinetics, Pyrimidines/administration & dosage, Pyrimidines/blood, Pyrimidines/chemistry, Pyrimidines/pharmacokinetics, Pyrimidinones/administration & dosage, Pyrimidinones/blood, Pyrimidinones/chemistry, Pyrimidinones/pharmacokinetics, Reproducibility of Results, Sulfonamides/administration & dosage, Sulfonamides/blood, Sulfonamides/chemistry, Sulfonamides/pharmacokinetics, Tandem Mass Spectrometry/methods, Drug monitoring, LC-MS/MS, Targeted anticancer therapy, Tyrosine kinase inhibitor
Pubmed
Web of science
Création de la notice
12/02/2018 7:07
Dernière modification de la notice
20/08/2019 16:11
Données d'usage