LCMS Proteomics of Enzymes and Transporters: Practical Assessment and Theoretical Applications

Abstract

Abstract 15 Abstract Drug metabolizing enzymes and drug transporters interact to play a considerable role in drug disposition. Although the role of enzymes and their ontogenic profiles in adults has been detailed in many publications, there are still limited research efforts outlining transporter progression and ontogeny from childhood and onwards. This information is of a great value in enriching PBPK models which enable the prediction of therapeutic compounds’ behaviour especially in paediatric population. Due to the physiological and anatomical resemblance between pigs and humans, pigs are extensively used as research animals. For this, qualitative and quantitative information of transporters and enzymes in pigs, and their comparison with human values are of great importance. Mass spectrometry methods are known of their high sensitivity and selectivity, therefore, they may be of enormous value especially with the very limited size and availability of paediatric samples, and also for the difficulty associated with isolation of transporters and other proteins from biological membranes. QconCAT is a protein standard formed from proteotypic peptides that enables the quantification of about 50 of transporters and enzymes at the same time with high degree of robustness.

Date of Award	31 Dec 2018
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Jill Barber (Supervisor) & Amin Rostami-Hochaghan (Supervisor)