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