Identification of Xenobiotic Biotransformation Products Using Mass Spectrometry-Based Metabolomics Integrated with a Structural Elucidation Strategy by Assembling Fragment Signatures.
Anal Chem
; 95(38): 14279-14287, 2023 09 26.
Article
em En
| MEDLINE
| ID: mdl-37713273
ABSTRACT
The identification of xenobiotic biotransformation products is crucial for delineating toxicity and carcinogenicity that might be caused by xenobiotic exposures and for establishing monitoring systems for public health. However, the lack of available reference standards and spectral data leads to the generation of multiple candidate structures during identification and reduces the confidence in identification. Here, a UHPLC-HRMS-based metabolomics strategy integrated with a metabolite structure elucidation approach, namely, FragAssembler, was proposed to reduce the number of false-positive structure candidates. biotransformation product candidates were filtered by mass defect filtering (MDF) and multiple-group comparison. FragAssembler assembled fragment signatures from the MS/MS spectra and generated the modified moieties corresponding to the identified biotransformation products. The feasibility of this approach was demonstrated by the three biotransformation products of di(2-ethylhexyl)phthalate (DEHP). Comprehensive identification was carried out, and 24 and 13 biotransformation products of two xenobiotics, DEHP and 4'-Methoxy-α-pyrrolidinopentiophenone (4-MeO-α-PVP), were annotated, respectively. The number of 4-MeO-α-PVP biotransformation product candidates in the FragAssembler calculation results was approximately 2.1 times lower than that generated by BioTransformer 3.0. Our study indicates that the proposed approach has great potential for efficiently and reliably identifying xenobiotic biotransformation products, which is attributed to the fact that FragAssembler eliminates false-positive reactions and chemical structures and distinguishes modified moieties on isomeric biotransformation products. The FragAssembler software and associated tutorial are freely available at https//cosbi.ee.ncku.edu.tw/FragAssembler/ and the source code can be found at https//github.com/YuanChihChen/FragAssembler.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dietilexilftalato
/
Espectrometria de Massas em Tandem
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Revista:
Anal Chem
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Taiwan