Journal
CLINICA CHIMICA ACTA
Volume 485, Issue -, Pages 298-304Publisher
ELSEVIER
DOI: 10.1016/j.cca.2018.07.009
Keywords
Entrectinib; Quantification; LC-MS/MS; Human plasma; Metabolic degradation assessment; Rat liver microsomes
Categories
Funding
- Deanship of Scientific Research at the King Saud University [RGP-322]
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Entrectinib (ENC) is a potent orally available anaplastic lymphoma kinase (ALK) inhibitor. In 10 July 2017, biotechnology company (Ignyta) announced that granted orphan drug designation approval was given by the FDA to ENC for treatment of NTRK fusion-positive solid tumors. A validated LC-MS/MS methodology was developed for ENC quantification in human plasma matrix. The supposed method characterized by high speed, specificity and sensitivity. This established method was applied for metabolic degradation assessment of ENC. Reversed stationary phase (C-18 column) and elution mobile phase (48% 10 mM ammonium formate in H2O (pH: 4.2 adjusted by adding few drops of formic acid): 52% ACN) were utilized for chromatographic resolution of ENC and lapatinib as internal standard (IS). Total elution time, flow rate and injection volume were 4 min., 0.25 mL/min., and 5 mu L, respectively. Electrospray ionization source was used for ions generation, while positive multiple reactions monitoring (MRM) mode was used for ion analysis. The data of calibration curve of ENC in human plasma was linear in the range of 5-500 ng/mL with correlation coefficient (r(2)) > 0.999. LOQ and LOD for ENC were 2.17 ng/mL and 0.71 ng/mL, respectively. Inter-day and intra-day precision and accuracy were 97.52 to 101.83%, and 0.38 to 1.32%, respectively. Intrinsic clearance (Clint) and in vitro half-life (t(1/2)) were equal to 15.67 mL/min/kg and 9.1 min, respectively. To our knowledge, this is considered the first method for ENC quantification in human plasma and its metabolic degradation assessment.
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