Identification of Phase II Isomeric Metabolites of Paracetamol by Ion Mobility

• Grant number: 24/09983-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Thiago Carita Correra
• Grantee: James Lee
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/06726-0 - Investigation of reactive intermediates in complex chemical and biochemical processes, AP.JP2

Abstract

This study aims to evaluate the isomeric Phase II metabolites of paracetamol metabolism using ion mobility spectrometry coupled with mass spectrometry. Understanding drug metabolism is essential for monitoring treatments and ensuring drug safety. Knowledge of the formed metabolites allows for the analysis of potential adverse effects and is an important step in the development of new treatments.Mass spectrometry is a highly advantageous technique for characterizing metabolites in complex matrices, but for the determination of the many isomers that can be formed in Phases I and II of metabolism, other advanced coupled techniques are required for unequivocal determination. Therefore, this project will apply the differential ion mobility technique (FAIMS) to separate the isomers formed by online electrochemical methods that mimic phases I and II of metabolism. Since the formed metabolites often lack analytical standards due to their high reactivity and difficulty in preparation, ion vibrational spectroscopy (IRMPD) will be used to characterize the species separated by ion mobility.Thus, this project aims not only to implement methodologies for the formation of Phase I and II metabolites of paracetamol but also to apply isomer characterization techniques for the unequivocal identification of the formed species.It is worth noting that paracetamol was chosen not only for its relevance as a drug but also because of the large number of studies for the identification of its metabolites. Thus, this drug can be used as a model for the implementation of the proposed methodologies, opening the possibility to study various other drugs in the future.