ArticleJournal of proteome research2013
Stable isotope- and mass spectrometry-based metabolomics as tools in drug metabolism: a study expanding tempol pharmacology.
Article in Journal of proteome research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- 2,8-Dihydroxyquinoline ameliorates oligoasthenozoospermia by inhibiting MAPK14-mediated spermatogonial ferroptosis.Molecular biology reports · 2026Article
- Isolation and Identification of Aryl Hydrocarbon Receptor Modulators in White Button Mushrooms (Journal of agricultural and food chemistry · 2019Article
- Microbiota Metabolism Promotes Synthesis of the Human Ah Receptor Agonist 2,8-Dihydroxyquinoline.Journal of proteome research · 2019Article
- Application of Metabolomics in the Study of Natural Products.Natural products and bioprospecting · 2018Article
- Metabolic map of osthole and its effect on lipids.Xenobiotica; the fate of foreign compounds in biological systems · 2018Article
- Analysis of stable isotope assisted metabolomics data acquired by GC-MS.Analytica chimica acta · 2017Article
- Intestinal Farnesoid X Receptor Signaling Modulates Metabolic Disease.Digestive diseases (Basel, Switzerland) · 2017Review
- An Intestinal Microbiota-Farnesoid X Receptor Axis Modulates Metabolic Disease.Gastroenterology · 2016Review
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- Transgenic mice and metabolomics for study of hepatic xenobiotic metabolism and toxicity.Expert opinion on drug metabolism & toxicology · 2015Review
- Modulation of colon cancer by nutmeg.Journal of proteome research · 2015Article
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- Untargeted profiling of tracer-derived metabolites using stable isotopic labeling and fast polarity-switching LC-ESI-HRMS.Analytical chemistry · 2014Article
- LC-MS-based metabolomics: an update.Archives of toxicology · 2014Review
- Lipidomics reveals a link between CYP1B1 and SCD1 in promoting obesity.Journal of proteome research · 2014Article
- Probing the influence of protecting groups on the anomeric equilibrium in sialic acid glycosides with the persistent radical effect.Journal of the American Chemical Society · 2014Article
- Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity.Nature communications · 2013Article
- Article
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10 authors at 5 institutions in 1 country.
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Abstract
The application of mass spectrometry-based metabolomics in the field of drug metabolism has yielded important insights not only into the metabolic routes of drugs but has provided unbiased, global perspectives of the endogenous metabolome that can be useful for identifying biomarkers associated with mechanism of action, efficacy, and toxicity. In this report, a stable isotope- and mass spectrometry-based metabolomics approach that captures both drug metabolism and changes in the endogenous metabolome in a single experiment is described. Here the antioxidant drug tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) was chosen because its mechanism of action is not completely understood and its metabolic fate has not been studied extensively. Furthermore, its small size (MW = 172.2) and chemical composition (C(9)H(18)NO(2)) make it challenging to distinguish from endogenous metabolites. In this study, mice were dosed with tempol or deuterated tempol (C(9)D(17)HNO(2)) and their urine was profiled using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Principal component analysis of the urinary metabolomics data generated a Y-shaped scatter plot containing drug metabolites (protonated and deuterated) that were clearly distinct from the endogenous metabolites. Ten tempol drug metabolites, including eight novel metabolites, were identified. Phase II metabolism was the major metabolic pathway of tempol in vivo, including glucuronidation and glucosidation. Urinary endogenous metabolites significantly elevated by tempol treatment included 2,8-dihydroxyquinoline (8.0-fold, P < 0.05) and 2,8-dihydroxyquinoline-β-d-glucuronide (6.8-fold, P < 0.05). Urinary endogenous metabolites significantly attenuated by tempol treatment including pantothenic acid (1.3-fold, P < 0.05) and isobutrylcarnitine (5.3-fold, P < 0.01). This study underscores the power of a stable isotope- and mass spectrometry-based metabolomics in expanding the view of drug pharmacology.
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