Effects of cotinine on information processing in nonsmokers

 Cotinine, the major proximate metabolite of nicotine, is present in smokers in higher concentrations and for a longer time than nicotine, yet its effects on information processing have not previously been reported. We studied the cognitive effects of cotinine in non-smokers. Sixteen subjects were tested on three doses of cotinine (0.5, 1.0, and 1.5 mg cotinine base/kg), and placebo, on a choice reaction time (RT) task and on a verbal recall task with short and long lists. Cotinine significantly impaired recall on the long list and displayed non-significant but generally consistent dose-related slowing of RT and N100 latency. The acute effects of cotinine were small, and probably do not account for the cognitive deficits observed in tobacco withdrawal, although the cognitive effects of chronic cotinine administration need to be investigated. Received: 2 January 1997/Final version: 22 June 1997     

Effects of nicotine and cotinine on bovine theca interna and granulosa cells

The purpose of this study was to determine if nicotine or cotinine inhibits steroidogenesis in the ovarian follicle. Theca interna and granulosa cells were isolated from bovine follicles, cultured with nicotine or cotinine for 24 h, and culture media were assayed for androstenedione or estradiol. Treatment of theca interna with 6, 60, and 600 μM nicotine decreased (P≤0.002) production of androstenedione to 55, 53, and 24% of control levels, respectively. Levels of androstenedione in theca interna treated with cotinine were not different from control values. In granulosa cells, nicotine inhibited production of estradiol at the highest dose tested. Treatment with 600 μM nicotine decreased (P≤0.001) estradiol concentration to 12% of control values, attributable to a general cytotoxic effect. Cotinine had no effect on estradiol production by granulosa cells. These results provide novel evidence for inhibitory effects of nicotine on androgen production by theca interna.     

Exposure to Environmental Tobacco Smoke among Infants in Southern Thailand: A Study of Urinary Cotinine

We performed a survey to assess the exposure to environmental tobacco smoke (ETS) in 1-year-old infants in Thailand. Of the 725 infants, it was reported that 73.3% had household smoking and 40.7% had detectable urinary cotinine. Twenty-five infants (3.4%) had urinary cotinine in the range of adult heavy smokers. The prevalence of ETS exposure was significantly higher in infants with a father whose education was ≤ grade 6 than in those with father’s education >6 years (44.0% vs. 36.0%, p = 0.039). Data on the exposure to ETS among infants will provide prevalence information and identify population subgroups at increased risk for exposure.     

Calculating summary statistics for population chemical biomonitoring in women of childbearing age with adjustment for age-specific natality

The effects of chemical exposures during pregnancy on children’s health have been an increasing focus of environmental health research in recent years, leading to greater interest in biomonitoring of chemicals in women of childbearing age in the general population. Measurements of mercury in blood from the National Health and Nutrition Examination Survey are frequently reported for “women of childbearing age,” defined to be of ages 16–49 years. The intent is to represent prenatal chemical exposure, but blood mercury levels increase with age. Furthermore, women of different ages have different probabilities of giving birth. We evaluated options to address potential bias in biomonitoring summary statistics for women of childbearing age by accounting for age-specific probabilities of giving birth. We calculated median and 95th percentile levels of mercury, PCBs, and cotinine using these approaches: option 1: women aged 16–49 years without natality adjustment; option 2: women aged 16–39 years without natality adjustment; option 3: women aged 16–49 years, adjusted for natality by age; option 4: women aged 16–49 years, adjusted for natality by age and race/ethnicity. Among the three chemicals examined, the choice of option has the greatest impact on estimated levels of serum PCBs, which are strongly associated with age. Serum cotinine levels among Black non-Hispanic women of childbearing age are understated when age-specific natality is not considered. For characterizing in utero exposures, adjustment using age-specific natality provides a substantial improvement in estimation of biomonitoring summary statistics.     

Determination of nicotine,cotinine, and related alkaloids in human urine and saliva by automated in-tube solid-phase microextraction coupled with liquid chromatography–mass spectrometry

A simple, rapid and sensitive method for the determination of nicotine, cotinine, nornicotine, anabasine, and anatabine in human urine and saliva was developed. These compounds were analyzed by on-line in-tube solid-phase microextraction (SPME) coupled with liquid chromatography–mass spectrometry (LC–MS). Nicotine, cotinine and related alkaloids were separated within 7 min by high performance liquid chromatography (HPLC) using a Synergi 4u POLAR-RP 80A column and 5 mM ammonium formate/methanol (55/45, v/v) as a mobile phase at a flow-rate of 0.8 mL/min. Electrospray ionization conditions in the positive ion mode were optimized for MS detection of these compounds. The optimum in-tube SPME conditions were 25 draw/eject cycles with a sample size of 40 μL using a CP-Pora PLOT amine capillary column as the extraction device. The extracted compounds could be desorbed easily from the capillary by passage of the mobile phase, and no carryover was observed. Using the in-tube SPME LC–MS method, the calibration curves were linear in the concentration range of 0.5–20 ng/mL of nicotine, cotinine and related compounds in urine and saliva, and the detection limits (S/N = 3) were 15–40 pg/mL. The method described here showed 20–46-fold higher sensitivity than the direct injection method (5 μL injection). The within-run and between-day precision (relative standard deviations) were below 4.7% and 11.3% (n = 5), respectively. This method was applied successfully to analysis of urine and saliva samples without interference peaks. The recoveries of nicotine, cotinine and related compounds spiked into urine and saliva samples were above 83%, and the relative standard deviations were below 7.1%. This method was used to analyze urinary and salivary levels of these compounds in nicotine intake and smoking.     

同位素稀释-超高效反相液相色谱串联质谱测定尿中尼古丁和可替尼

目的 建立尿液中尼古丁和可替尼的超高效液相色谱-串联质谱（UPLC-MS/MS）测定方法。方法 尿样经含有同位素标记的尼古丁-d3与可替尼-d3的水稀释后,引入UPLC-MS/MS分离分析。以Waters ACQUITY UPLC HSS T3 C¹8色谱柱(50mm×3.0mm, 1.8μm)为分离柱,甲醇和0.1%氨水作流动相,梯度洗脱,流速为0.2ml/min;以正离子扫描多反应监测模式检测,用内标校正法定量。结果 尼古丁和可替尼在1.0～1000ng/ml浓度内线性良好,方法检出限分别为0.28和0.32ng/ml;定量限分别为0.93和0.98ng/ml;加标回收率分别为86.3%～101%和81.2%～102%,相对标准偏差分别为1.08%~6.01%和1.22%~2.33%。结论 本法快速、灵敏,操作便捷,定量准确,可为人群烟草暴露情况的调查提供检测方法。     

Long-term nicotine substitution after application of a 16-hour nicotine patch in smoking cessation

Summary The purpose of the study was to examine long-term nicotine substitution and its variability during use of a nicotine patch. In two smoking cessation studies a 16-h nicotine patch, releasing 15 mg nicotine, was applied daily for 16 h over 12 weeks, to 167 smokers. Salivary cotinine was highly correlated with plasma cotinine (r = 0.93), and the concentration of cotinine in a single sample in the afternoon was well correlated with the AUC_cotinine over 24 h (r = 0.94). The salivary cotinine concentration after 1 week in 60 abstainers was 183 ng · ml^–. After 3, 6 and 12 weeks the cotinine concentrations were 86%, 79% and 59% of the 1-week value. The degree of nicotine compensation attained by the patch after 1 week was 52% (SD 24%) in subjects who succeeded in stopping smoking for at least 3 weeks. A quarter of the subjects achieved a compensation of less than 35% of their usual nicotine intake. Nicotine substitution with this 16-h nicotine patch was stable and the risk of overcompensation was small in this group of smokers.     

Smoking characteristics and inhalation biochemistry in the Scottish population

Data from a cross-sectional random population sample of 10,359 middleaged Scottish men and women are used to investigate the relationships between self-reported tobacco consumption and three biochemical markers of tobacco inhalation: expired air carbon monoxide (CO), serum thiocyanate and serum cotinine. These data represent one of the largest samples of these biochemical markers yet analysed. The results show that, for each sex, the biochemical markers are highly correlated for smokers and for the entire sample of mixed smokers and non-smokers. CO is the preferred biochemical marker, in such groups, because it is the cheapest, is non-invasive and gives virtually instantaneous results. Self-reported daily cigarette consumption also correlates well with each of these biochemical markers, and so it appears that people are, in the context of population studies, mainly truthful about their smoking. The relationships with self-reported cigarette consumption are curvilinear with apparent levelling out of the gradient at around 25 cigarettes/day for cotinine and thiocyanate and at 40 cigarettes/day for CO. Sex differences are small, although thiocyanate is generally higher and cotinine generally lower in women with the same self-reported cigarette consumption as men. Amongst non-smokers, only cotinine is able to discriminate between self-reported levels of exposure to passive smoking. CO and thiocyanate are not suitable for measuring low levels of smoke inhalation, such as found in passive smokers.