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

AI Article Synopsis

  • The study aimed to enhance the efficiency of drug-drug interaction assays using HPLC-high-resolution mass spectrometry (HPLC-HRMS) with polarity switching.
  • The analysis involved microsomal incubates and used a Q-Exactive mass spectrometer to gather both qualitative and quantitative data from the samples.
  • Results indicated that the method successfully quantified multiple probe compounds and revealed that LOR inhibited CYP2C19 while increasing activity for CYP2D6, CYP2E1, and CYP3A4, ultimately improving throughput in drug interaction assays.

Article 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.

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Source
http://dx.doi.org/10.4155/bio-2018-0019DOI Listing

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