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

Bioanalysis. 2018 May 1;10(9):659-671. doi: 10.4155/bio-2018-0019. Epub 2018 May 11.

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: CYP inhibition; LC–HRMS full scan; cocktail assay; drug–drug interaction; loratadine.

Publication types

  • Evaluation Study

MeSH terms

  • Administration, Oral
  • Chromatography, High Pressure Liquid / methods
  • Cytochrome P-450 Enzyme Inhibitors / administration & dosage*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Data Accuracy
  • Drug Evaluation, Preclinical
  • Drug Interactions
  • High-Throughput Screening Assays / methods*
  • Humans
  • Loratadine / administration & dosage*
  • Mass Spectrometry / methods
  • Microsomes, Liver / drug effects*
  • Microsomes, Liver / enzymology
  • Reference Standards

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Loratadine
  • Cytochrome P-450 Enzyme System