HPLC-high-resolution mass spectrometry with polarity switching for increasing throughput of human in vitro cocktail drug-drug interaction assay

Ragu Ramanathan, Anima Ghosal, Lakshmi Ramanathan, Kate Comstock, Helen Shen, Dil Ramanathan

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Pages (from-to)659-672
Number of pages14
JournalBioanalysis
Volume10
Issue number9
DOIs
StatePublished - 2018

Keywords

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

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