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Quantifying vemurafenib in dried blood spots using high-performance LC-MS/MS
Cynthia M Nijenhuis1, Hilde Rosing, Jan H M Schellens
1Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Bioanalysis
|December 23, 2014
Summary
A new LC-MS/MS method quantifies vemurafenib in dried blood spots for therapeutic drug monitoring. This validated assay supports pharmacokinetic studies and patient treatment in melanoma care.
Area of Science:
- Analytical Chemistry
- Pharmacology
- Biochemistry
Background:
- Vemurafenib pharmacokinetics require further investigation.
- Therapeutic drug monitoring (TDM) is crucial for optimizing vemurafenib treatment.
- Dried blood spots (DBS) offer a minimally invasive matrix for drug analysis.
Purpose of the Study:
- Develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.
- Quantify vemurafenib concentrations in dried blood spots.
- Support pharmacokinetic studies and TDM of vemurafenib.
Main Methods:
- Extraction of vemurafenib from DBS using methanol:acetonitrile (50:50, v/v).
- Separation on a C18 column with gradient elution.
- Analysis using triple quadrupole mass spectrometry in positive ion mode.
Main Results:
- The method demonstrated linearity from 1 to 100 µg/ml.
- Intra- and inter-assay accuracies were within ±13.6%.
- Intra- and inter-assay precisions were ≤6.5%.
Conclusions:
- The developed LC-MS/MS assay meets all validation criteria.
- The assay is suitable for quantifying vemurafenib in DBS.
- This method can be applied to analyze samples from melanoma patients undergoing vemurafenib therapy.
