Using a high-resolution mass spectrometry-based metabolomics strategy for comprehensively screening and identifying biomarkers of phthalate exposure: Method development and application

Identification of Xenobiotic Biotransformation Products Using Mass Spectrometry-Based Metabolomics Integrated with a Structural Elucidation Strategy by Assembling Fragment Signatures

“…The other 5 biotransformation products (M17 ∼ M21) were identified as dihydroxylation products. The dihydroxylation of phthalate was also described in a reported publication investigating the biotransformation product identification for another phthalate, di­(2-propylheptyl) phthalate (DPHP), and the dihydroxylation product was considered a sensitive exposure marker …”

“…For example, 5-hydroxydiclofenac, a metabolite of diclofenac, is associated with hepatocyte cytotoxicity, and the reactive metabolites of polycyclic aromatic hydrocarbons (PAHs) have been confirmed to have carcinogenic properties . Since xenobiotic biotransformation products have crucial health impacts, the identification of these compounds is necessary and has attracted research attention in the context of drug development, − the discovery of biomarkers for biomonitoring, − and forensic toxicology. , …”

“…UHPLC-HRMS provides an omics-scale tool to simultaneously measure a vast number of chemical features in samples of interest. Using UHPLC-HRMS-based untargeted metabolomics, the features of biotransformation products can be comprehensively filtered from complicated backgrounds with diverse approaches, such as stable isotope tracing, mass defect filtering (MDF), time-dependent methods, concentration–response design, and similarities between the MS/MS spectra of the parent compound and its biotransformation products. ,,− However, the enormous number of unknown features also enhances the requirement for reliable structural identification approaches. The lack of availability of standards and reference MS/MS data for most xenobiotic biotransformation products limits the application of high-confidence structural identification methods, such as reference standard-based confirmation and library spectrum matching …”

Connecting chemical exposome to human health using high‐resolution mass spectrometry‐based biomonitoring: Recent advances and future perspectives

“…An appropriate statistical procedure is usually chosen by the study design of an untargeted biomonitoring investigation. For instance, the significant features between the low and the high-exposure groups can be discovered by t test and orthogonal partial least squares discriminant analysis (OPLS-DA) (J.-F. Hsu et al, 2019). Furthermore, the significant features among multiple groups can be analyzed by analysis of variance (ANOVA), principal components analysis (PCA), or partial least squares discriminant analysis (PLS-DA) with graphical visualization (Pan et al, 2021).…”

Hair Metabolomics in Animal Studies and Clinical Settings

“…Metabolomics, a holistic analytical approach to studying metabolomes, is a powerful tool in understanding the comprehensive changes in metabolic responses in living systems induced by external stimuli or genetic alterations and is the endpoint of the omics cascade [2,3,4,5]. Unlike genomics, transcriptomics, and proteomics, metabolomics reflects the phenotype of living things, enabling us to observe simultaneous changes in many metabolites, thus aiding the discovery of biomarkers for disease diagnosis and facilitating the determination of the metabolic effects on toxicity and the exploration of the action mechanisms in pathogenesis [6,7,8,9,10,11,12,13]. The number of papers published concerning metabolomics and biomarkers has increased exponentially over the past several years.…”