Murdoch University Research Repository

Welcome to the Murdoch University Research Repository

The Murdoch University Research Repository is an open access digital collection of research
created by Murdoch University staff, researchers and postgraduate students.

Learn more

Hybrid organic/inorganic hybrid surface technology for increasing the performance of LC/MS(MS)-based drug metabolite identification studies: Application to gefitinib and metabolites in mouse plasma and urine

Plumb, R.S., Gethings, L.A., King, A., Mullin, L.G., Maker, G.ORCID: 0000-0003-1666-9377, Trengove, R. and Wilson, I.D. (2021) Hybrid organic/inorganic hybrid surface technology for increasing the performance of LC/MS(MS)-based drug metabolite identification studies: Application to gefitinib and metabolites in mouse plasma and urine. Journal of Pharmaceutical and Biomedical Analysis, 200 . Art. 114076.

Link to Published Version: https://doi.org/10.1016/j.jpba.2021.114076
*Subscription may be required

Abstract

The detection, identification and quantification of drug metabolites plays a key role in drug discovery and development. Liquid chromatography (LC) coupled to mass spectrometry (MS) has become the primary technology for these studies due to its sensitivity and specificity. However, the presence of transition metals in the chromatography system and columns can result in non-specific and unwanted interactions with the drug and/or its metabolites, via electron-pair donation, leading to poor chromatography and analyte loss. The use of a hybrid organic/inorganic surface applied to the metal surfaces of the chromatography system and column has been demonstrated to reduce or eliminate these effects. When employed for the analysis of mouse urine, derived from the oral dosing of mice with the EGFR inhibitor gefitinib, we observed more symmetrical LC peaks. This resulted in a 33 % improvement in peak capacity for a 10 min reversed – phase gradient separation, a two-fold increase in MS response, cleaner MS spectra and improved peak response reproducibility. This hybrid surface barrier appears to offer significant advantages in the analysis of low-concentration metabolites, potentially facilitating the accurate determination of the elimination phase of the pharmacokinetic (PK) curve and detection of drug metabolites in microdosing or microsampling studies.

Item Type: Journal Article
Murdoch Affiliation(s): Centre for Computational and Systems Medicine
Health Futures Institute
Separation Science and Metabolomics Laboratory
Publisher: Elsevier
Copyright: © 2021 Elsevier B.V.
URI: http://researchrepository.murdoch.edu.au/id/eprint/60612
Item Control Page Item Control Page