To avoid the potential variability in NMR related to non steady-state levels of cotinine derived from natural nicotine in light and intermittent smokers, deuterium-labeled cotinine (cotinine-d4) was administered (30). Using this technique, it was possible to reliably capture the rate of nicotine clearance in very light intermittent smokers. Importantly, there is no difference in the metabolic breakdown of natural cotinine and labeled cotinine (e.g., cotinine-d4) and neither is affected by the presence or absence of nicotine (31). The use of deuterium-labeled cotinine allowed similar comparisons across all levels of smoking since we only measured the labeled cotinine and its labeled metabolite.
