Title

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

Authors

Ragu Ramanathan, Pfizer Inc.
Anima Ghosal, Kean University
Lakshmi Ramanathan, QPS, LLC
Kate Comstock, Thermo Fisher Scientific Inc.
Helen Shen, QPS, LLC
Dil Ramanathan, Kean University

Document Type

Article

Publication Date

1-1-2018

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.

Publication Title

Bioanalysis

First Page Number

659

Last Page Number

672

DOI

10.4155/bio-2018-0019

Recommended Citation

Ramanathan, Ragu; Ghosal, Anima; Ramanathan, Lakshmi; Comstock, Kate; Shen, Helen; and Ramanathan, Dil, "HPLC-high-resolution mass spectrometry with polarity switching for increasing throughput of human in vitro cocktail drug-drug interaction assay" (2018). Kean Publications. 1551.
https://digitalcommons.kean.edu/keanpublications/1551