Reproducibility of the Nicotine Metabolite Ratio in Cigarette Smokers
Bibliographic record
Abstract
BACKGROUND: The nicotine metabolite ratio (NMR or 3-hydroxycotinine/cotinine) has been used to phenotype CYP2A6-mediated nicotine metabolism. Our objectives were to analyze (i) the stability of NMR in plasma, saliva, and blood in various storage conditions, (ii) the relationship between NMRs derived from blood, plasma, saliva, and urine, and (iii) the reproducibility of plasma NMR in ad libitum cigarette smokers. METHODS: We analyzed data from four clinical studies. In studies 1 and 2, we assessed NMR stability in saliva and plasma samples at room temperature (~22°C) over 14 days and in blood at 4°C for up to 72 hours. In studies 2 and 3, we used Bland-Altman analysis to assess agreement between blood, plasma, saliva, and urine NMRs. In study 4, plasma NMR was measured on six occasions over 44 weeks in 43 ad libitum smokers. RESULTS: Reliability coefficients for stability tests of NMR in plasma and saliva at room temperature were 0.97 and 0.98, respectively, and 0.92 for blood at 4°C. Blood NMR agreed consistently with saliva and plasma NMRs but showed more variability in relation to urine NMR. The reliability coefficient for repeated plasma NMR measurements in smokers was 0.85. CONCLUSION: The NMR is stable in blood, plasma, and saliva at the conditions tested. Blood, plasma, and saliva NMRs are similar whereas urine NMR is a good proxy for these NMR measures. Plasma NMR was reproducible over time in smokers. IMPACT: One measurement may reliably estimate a smoker's NMR for use as an estimate of the rate of nicotine metabolism.
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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 | 0.009 | 0.002 |
| 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 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".