CYP2D6-Dependent Bufuralol 1 '-Hydroxylation Assayed by Reversed-Phase Ion-Pair High-Performance Liquid Chromatography with Fluorescence Detection
Bibliographic record
Abstract
CYP2D6 is an enzyme that is subject to genetic polymorphism 1. This P450 is absent in individuals with the poor metabolizer CYP2D6 phenotype 2, 3), resulting in a substantially reduced capacity to metabolize a large number of clinically useful drugs, including metoprolol, propafenone, haloperrdol, dextromethorphan and codeine (1). Quinidine competrtively inhibits CYP2D6, with a K1 of 3-30 mM (3–5). Because of its preferential inhibition of CYP2D6 (6 7), quinidine is frequently used as an inhibitory chemical probe of this polymorphically expressed P450. Diagnostic catalytic monitors of human hepatic CYP2D6 include debrisoquine 4-hydroxylase (4), dextromethorphan Odemethylase (8), and bufuralol l’-hydroxylase activities (2–4). Advantages of using bufuralol as a CYP2D6-selective substrate include the high sensitivity of the assay owing to the highly fluorescent l’-hydroxybufuralol metabohte and the fact that the use of radiolabeled substrate is not required. This chapter describes a modification of a reversed-phase ion-pair high-performance liquid chromatographic (HPLC) assay (9) with fluorescence detection for the determmation of bufuralol l’-hydroxylation activity. Methods for other CYP2D6 assays such as debrisoquine 4-hydroxylase (9) and dextromethorphan O-demethylase (9, 10) can be found in the cited references.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 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 | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 teacher head, 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".