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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
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