An UPLC-MS/MS method for the quantification of BRAF inhibitors (vemurafenib, dabrafenib) and MEK inhibitors (cobimetinib, trametinib, binimetinib) in human plasma. Application to treated melanoma patients.
Clin Chim Acta
; 470: 8-13, 2017 Jul.
Article
in En
| MEDLINE
| ID: mdl-28412197
ABSTRACT
Targeted therapies for cancers are fast-growing therapies. For instance kinase inhibitors such as BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) are increasingly used to treat malignant melanoma. The metabolic profile of these drugs can result in great interindividual variability, justifying therapeutic drug monitoring (TDM). We describe a rapid and specific method for quantification of 2 BRAFi (vemurafenib, dabrafenib) and 3 MEKi (cobimetinib, trametinib and binimetinib). Chromatography was performed on a Waters Acquity-UPLC system with CORTECS C18+ column, under a gradient of 10% acetic acid in water/acetonitrile. An Acquity-TQD® with electrospray ionization was used for detection. Samples were prepared by solid phase extraction (Oasis® MCX microElution) before injection in the system. Calibration curves ranges from 0.4 to 100µg/ml for vemurafenib, from 1 to 1000ng/ml for dabrafenib, from 0.5 to 500ng/ml for cobimetinib and binimetinib, and from 0.75 to 250ng/ml for trametinib. At all concentrations the bias was within ±15% of the nominal concentrations and precision was ≤15%. All results were within the acceptance criteria of the EMA guidelines on method validation. This rapid, sensitive and specific UPLC-MS/MS method can perform simultaneous quantification of targeted therapies used in malignant melanoma and is usable for routine TDM.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromatography, High Pressure Liquid
/
Mitogen-Activated Protein Kinase Kinases
/
Proto-Oncogene Proteins B-raf
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Protein Kinase Inhibitors
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Tandem Mass Spectrometry
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Melanoma
Type of study:
Guideline
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Clin Chim Acta
Year:
2017
Document type:
Article