2. Academic Validation
  3. Investigation of metabolic stability of the novel ALK inhibitor brigatinib by liquid chromatography tandem mass spectrometry

Investigation of metabolic stability of the novel ALK inhibitor brigatinib by liquid chromatography tandem mass spectrometry

  • Clin Chim Acta. 2018 May;480:180-185. doi: 10.1016/j.cca.2018.02.016.
Hany W Darwish 1,  Adnan A Kadi 2,  Mohamed W Attwa 3,  Halah S Almutairi 4
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt. Electronic address: hdarwish@ksu.edu.sa.
  • 2 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: akadi@ksu.edu.sa.
  • 3 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: mzeidan@ksu.edu.sa.
  • 4 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: alhalah@ksu.edu.sa.
PMID: 29458050 DOI: 10.1016/j.cca.2018.02.016
Abstract

Brigatinib (BGB) belongs to a class of drugs called ALK inhibitor. On April 28, 2017, BGB has been approved by U.S. FDA for use in metastatic ALK-positive NSCLC. A fast, specific, sensitive and validated LC-MS/MS method was developed for the quantification of BGB in human plasma matrix. This method was applied successfully to study metabolic stability of BGB. Reversed phase (C18 column) and isocratic binary mobile phase (55% 0.1% formic acid: 45% ACN) were used for chromatographic separation of BGB and ponatinib (IS). The flow rate, total run time and injection volume were fixed at 0.2 mL/min, 4 min, 5 μL respectively. ESI source was utilized for ions formation, while multiple reaction monitoring (MRM) mode was used for ion analysis. In human plasma matrix, the Linearity range of the calibration curve was 5-500 ng/mL (r2 ≥ 0.9982). LOQ and LOD were found to be 1.89 and 5.72 ng/mL. The precision and accuracy for the intra-day and inter-day were 0.45 to 1.85% and 97.37 to 104.85%. In vitro half-life (t1/2) and intrinsic clearance (CLint) were equal to 12.0 min and 13.1 ± 0.15 mL/min/kg respectively. The quantification of BGB in human plasma or its metabolic stability has not been studied as seen in literature review.

Keywords

Brigatinib; Human plasma; LC-MS/MS; Metabolic stability estimation; Quantification; Rat liver microsomes.

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