Quantifying vemurafenib in dried blood spots using high-performance LC-MS/MS

Background: To further investigate the pharmacokinetics of vemurafenib and to support therapeutic drug monitoring an LC-MS/MS method was developed and validated for the quantification of vemurafenib in dried blood spots. Results: Vemurafenib was extracted from the dried blood spots by methanol:acetonitrile (50:50, v/v) and separated on a C18 column with gradient elution and analyzed with triple quadrupole mass spectrometry in positive ion mode. The validated calibration range is linear from 1 to 100 mu g/ml. Intra- and inter-assay accuracies and precisions were within +/- 13.6% and 6.5%. The applicability of the assay was tested by analyzing dried blood spots samples of melanoma patients receiving vemurafenib. Conclusion: This assay met all predefined validation criteria and is considered suitable to quantify vemurafenib in dried blood samples.