Table 1.
Successful application of UPLC-MS-based metabolomics in xenobiotic studies
| Number of metabolites discovered |
|||||
|---|---|---|---|---|---|
| Xenobiotic | Animal model | Before | After | Key finding | Reference(s) |
| Arecoline, arecaidine (areca nut) | Wild-type mice | 4 | 11 | Novel pathways for arecoline and arecaidine metabolism | (47) |
| Arecoline 1-oxide | Wild-type mice | N/A | 13 | New metabolic pathways not previously recorded | (48) |
| PhIP | Wild-type,CYP1A2-humanized, and Cyp1a2-null mice | 9 | 17 | Importance of CYP1A2 in PhIP metabolism | (49, 84) |
| Fenofibrate | Sprague-Dawley rats, cynomolgus monkey | 4 | 9 | New metabolic pathways of fenofibrate | (45, 66) |
| APAP | (1) Cyp2e1-null and wild-type mice, (2) Wild-type mice, [acetyl-2 H3 ] APAP or 2,3,5,6-[2H4] APAP | 7 | 10 | Advantage of using a deuterated compound to identify and validate xenobiotic metabolites | (46) |
| Aminoflavone | Wild-type, Cyp1a2-null, and CYP1A2-humanized mice | 1 | 13 | Main metabolite is N 5-hydroxylated; 3-hydroxylation is preferable in humans | (50) |
| thioTEPA | Wild-type mice, liver microsome incubations | 3 | 9 | New metabolic pathways of thioTEPA | (52) |
| Melatonin | Wild-type, Cyp1a2-null, and CYP1A2-humanized mice | 7 | 14 | No interspecies difference with regard to CYP1A2-mediated metabolism | (42) |
| Cyclophosphamide,ifosfamide | Wild-type mice | 18 | 23 | Completion of metabolic map to S-carboxymethyl-cysteine and thiodiglycolic acid | (43) |
Abbreviations: APAP, acetaminophen; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; thio TEPA, N,N′,N″-triethylenethiophowsphoramide; UPLC-MS, ultraperformance liquid chromatography-mass spectrometry.