Discovery, Biosynthesis, and Structure Elucidation of Metabolites of a Doping Agent and a Direct Analogue, Tetrahydrogestrinone and Gestrinone, Using Human Hepatocytes
Bibliographic record
Abstract
Tetrahydrogestrinone (18a-homo-pregna-4,9,11-trien-17beta-ol-3-one, THG) is an anabolic androgenic steroid sold to athletes as an undetectable performance enhancer. Being an unapproved substance, no legitimate in vivo human excretion studies could be performed to identify urinary markers of this doping agent. In vitro systems were used as an alternative approach to study the human metabolism of THG and the gestrinone analogue, which is a marketed drug. Incubations of both compounds in the presence of human hepatocytes led to formation of oxidative and glucuroconjugated metabolites. Microgram quantities of the major in vitro metabolites were biosynthesized using human hepatocytes, characterized by HPLC/MS/MS, and their structures elucidated by NMR. Due to high structure similarity, both THG and gestrinone had an analogous in vitro metabolic pathway leading to successive addition of a hydroxyl and a beta-glucuronic acid at C-18. This in vitro metabolite of gestrinone was consistent with a previously reported major but unknown human urinary metabolite. The structure of another metabolite of THG was proposed to be a glucuroconjugate of an oxidative product with a hydroxyl group most likely at C-16epsilon. In vitro information reported therein could significantly impact the identification of new urinary markers of THG for doping control purposes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".