HPLC–high-Resolution Mass Spectrometry with Polarity Switching for Increasing Throughput of Human in vitro Cocktail Drug–Drug Interaction Assay

Abstract

Aim: Evaluation of HPLC–high-resolution mass spectrometry (HPLC–HRMS) full scan with polarity switching for increasing throughput of human in vitro cocktail drug–drug interaction assay. Materials & methods: Microsomal incubates were analyzed using a high resolution and high mass accuracy Q-Exactive mass spectrometer to collect integrated qualitative and quantitative (qual/quant) data. Results: Within assay, positive-to-negative polarity switching HPLC–HRMS method allowed quantification of eight and two probe compounds in the positive and negative ionization modes, respectively, while monitoring for LOR and its metabolites. Conclusion: LOR-inhibited CYP2C19 and showed higher activity for CYP2D6, CYP2E1 and CYP3A4. Overall, LC–HRMS-based nontargeted full scan quantitation allowed to improve the throughput of the in vitro cocktail drug–drug interaction assay.

Keywords::

• cocktail assay
• CYP inhibition
• drug–drug interaction
• LC–HRMS full scan
• loratadine

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.