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D4-cortisol (9,11,12,12-[2H]4-cortisol) is a stable isotope-labeled (deuterated) analogue of the endogenous glucocorticoid hormone cortisol (hydrocortisone). It is widely utilized in clinical research as an in vivo diagnostic tracer to investigate cortisol kinetics, clearance, and tissue-specific metabolic pathways. Specifically, D4-cortisol serves as a probe to quantify the activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and type 2 (11β-HSD2). Upon administration, 11β-HSD2 converts D4-cortisol to D3-cortisone by removing the deuterium at the 11α position, which is subsequently reduced back to D3-cortisol by 11β-HSD1. By measuring the dilution and interconversion of these deuterated isotopomers using liquid chromatography-tandem mass spectrometry (LC-MS/MS), researchers can assess whole-body and regional glucocorticoid metabolism in metabolic and endocrine disorders.
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