Determination of cobimetinib in human plasma using protein precipitation extraction and high-performance liquid chromatography coupled to mass spectrometry.

Inhibition of MAP/ERK kinase (MEK) is a promising strategy to control the growth of tumors that are dependent on aberrant signaling in the MEK pathway. Cobimetinib (GDC-0973) (S)-[3,4-Difluoro-2-(2-fluoro-4-iodo-phenylamino)-phenyl]-((S)-3-hydroxy-3-piperidin-2-yl-azetidin-1-yl)-methanone) inhibits proliferation of a variety of human tumor cell lines by inhibiting MEK1 and MEK2. A specific high performance liquid chromatography-mass spectrometric assay was developed and validated for the determination of cobimetinib in human plasma. The overall mean recovery using protein precipitation extraction with acetonitrile was found to be 54.1%. The calibration curve was ranged from 0.20 to 100ng/mL. The LLOQ was sensitive enough to detect terminal phase concentrations of the drug. The intra- and inter-assay precision (%CV) was within 10.3% and 9.5% for cobimetinib. The assay accuracy (%RE) was within ±13.7% of the nominal concentration values for cobimetinib with the normal analytical QCs. The developed assay was successfully used to analyze the human plasma samples (for pharmacokinetic analysis) from clinical trials.

RCT Entities:   Population Interventions Outcomes