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

R.S. Plumb; L.A. Gethings; A. King; L.G. Mullin; G. Maker; R. Trengove; I.D. Wilson

doi:10.1016/j.jpba.2021.114076

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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 article

Peer reviewed

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

R.S. Plumb, L.A. Gethings, A. King, L.G. Mullin, G. Maker, R. Trengove and I.D. Wilson

Journal of Pharmaceutical and Biomedical Analysis, Vol.200, Article 114076

2021

DOI: https://doi.org/10.1016/j.jpba.2021.114076

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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.

Details

Title: 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
Authors/Creators: R.S. Plumb (Author/Creator) - Waters (United States)
L.A. Gethings (Author/Creator) - Waters (United States)
A. King (Author/Creator) - Scientific Operations, Waters Corporation, Stamford Ave, Wilmslow, Manchester, SK9 4AX, UK; Centre for Computational and Systems Medicine, Health Futures Institute, Murdoch University, South Street, Murdoch, WA, 6150, Australia.
L.G. Mullin (Author/Creator) - Waters (United States)
G. Maker (Author/Creator) - Murdoch University
R. Trengove (Author/Creator) - Murdoch University
I.D. Wilson (Author/Creator) - Imperial College London
Publication Details: Journal of Pharmaceutical and Biomedical Analysis, Vol.200, Article 114076
Publisher: Elsevier
Identifiers: 991005539973507891
Copyright: © 2021 Elsevier B.V.
Murdoch Affiliation: Centre for Computational and Systems Medicine; Health Futures Institute; Separation Science and Metabolomics Laboratory
Language: English
Resource Type: Journal article

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 2 Chemistry; 2.211 Mass Spectrometry; 2.211.990 Metabolomics
Web Of Science research areas: Chemistry, Analytical; Pharmacology & Pharmacy
ESI research areas: Pharmacology & Toxicology