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Variations in LC-MS methods for absolute quantification of cytochrome P450 and uridine 5’-diphospho-glucuronosyltransferase enzymes in human tissue: A comparative cost analysis

Hajar Al Feteisi, Brahim Achour, Jill Barber, and Amin Rostami-Hodjegan

In: DMDG GMP JOINT MEETING; 22 Oct 2014-24 Oct 2014; Espace St Martin, Paris. 2015.

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Abstract

The quantification of cytochrome P450 (P450) and uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes is important for in vitro-in vivo extrapolation (IVIVE) of xenobiotic clearance, which has become an integral part of drug development. The availability of different mass spectrometry-based techniques has revolutionized the scene of quantitative IVIVE. There are different mass spectrometry-based techniques used for quantitative proteomics, and as more laboratories are opting for the use of these methods, selecting the most appropriate tool is becoming a concern. Such selection is a complex matter of balancing cost and benefit for the specific focus of a given project. To date, there has been no systematic comparison of the advantages, limitations, and cost of the available quantitative LC-MS techniques relevant to the measurement of drug-metabolizing enzymes and transporters. For the first time, we attempt to determine the significance of cost of different LC-MS methods of quantitative analysis of these proteins and to present a framework to objectively assess the choice of the techniques.

Bibliographic metadata

Type of resource:
Content type:
Type of conference contribution:
Publication date:
Conference title:
DMDG GMP JOINT MEETING
Conference venue:
Espace St Martin, Paris
Conference start date:
2014-10-22
Conference end date:
2014-10-24
Abstract:
The quantification of cytochrome P450 (P450) and uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes is important for in vitro-in vivo extrapolation (IVIVE) of xenobiotic clearance, which has become an integral part of drug development. The availability of different mass spectrometry-based techniques has revolutionized the scene of quantitative IVIVE. There are different mass spectrometry-based techniques used for quantitative proteomics, and as more laboratories are opting for the use of these methods, selecting the most appropriate tool is becoming a concern. Such selection is a complex matter of balancing cost and benefit for the specific focus of a given project. To date, there has been no systematic comparison of the advantages, limitations, and cost of the available quantitative LC-MS techniques relevant to the measurement of drug-metabolizing enzymes and transporters. For the first time, we attempt to determine the significance of cost of different LC-MS methods of quantitative analysis of these proteins and to present a framework to objectively assess the choice of the techniques.

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:261936
Created by:
Al Feteisi, Hajar
Created:
30th March, 2015, 09:35:18
Last modified by:
Al Feteisi, Hajar
Last modified:
15th December, 2015, 07:42:41

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