HPLC–high-resolution mass spectrometry with polarity switching for increasing throughput of human in vitro cocktail drug–drug interaction assay-Reference-Cited by-同舟云学术

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

Published:2018-05-01 Issue:9 Volume:10 Page:659-672
ISSN:1757-6180
Container-title:Bioanalysis
language:en
Short-container-title:Bioanalysis

Author:

Ramanathan Ragu¹,Ghosal Anima²,Ramanathan Lakshmi³,Comstock Kate⁴,Shen Helen³,Ramanathan Dil²

Affiliation:

1. Pfizer, Inc., Pfizer World Wide Research & Development 445 Eastern Point Road, Groton, CT 06340, USA

2. STEM Department, Kean University, 1000 Morris Avenue, Union, NJ 07083, USA

3. DPMK Department, QPS, LLC, 110 Executive Drive, Suite 7, Newark, DE 19702, USA

4. ThermoFisher, San Jose, CA, USA

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.

Publisher

Future Science Ltd

Subject

Medical Laboratory Technology,Clinical Biochemistry,General Pharmacology, Toxicology and Pharmaceutics,General Medicine,Analytical Chemistry

Link

http://www.future-science.com/doi/pdf/10.4155/bio-2018-0019

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