[Show abstract][Hide abstract] ABSTRACT: Cigarette smoking remains a significant health threat for smokers and nonsmokers alike. Secondhand smoke (SHS) is intrinsically more toxic than directly inhaled smoke. Recently, a new threat has been discovered - Thirdhand smoke (THS) - the accumulation of SHS on surfaces that ages with time, becoming progressively more toxic. THS is a potential health threat to children, spouses of smokers and workers in environments where smoking is or has been allowed. The goal of this study is to investigate the effects of THS on liver, lung, skin healing, and behavior, using an animal model exposed to THS under conditions that mimic exposure of humans. THS-exposed mice show alterations in multiple organ systems and excrete levels of NNAL (a tobacco-specific carcinogen biomarker) similar to those found in children exposed to SHS (and consequently to THS). In liver, THS leads to increased lipid levels and non-alcoholic fatty liver disease, a precursor to cirrhosis and cancer and a potential contributor to cardiovascular disease. In lung, THS stimulates excess collagen production and high levels of inflammatory cytokines, suggesting propensity for fibrosis with implications for inflammation-induced diseases such as chronic obstructive pulmonary disease and asthma. In wounded skin, healing in THS-exposed mice has many characteristics of the poor healing of surgical incisions observed in human smokers. Lastly, behavioral tests show that THS-exposed mice become hyperactive. The latter data, combined with emerging associated behavioral problems in children exposed to SHS/THS, suggest that, with prolonged exposure, they may be at significant risk for developing more severe neurological disorders. These results provide a basis for studies on the toxic effects of THS in humans and inform potential regulatory policies to prevent involuntary exposure to THS.
PLoS ONE 01/2014; 9(1):e86391. DOI:10.1371/journal.pone.0086391 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The precise quantitation of smoking during pregnancy is difficult in retrospective studies. Routinely collected blood specimens from newborns, stored as dried blood spots, may provide a low-cost method to objectively measure maternal smoking close to the time of delivery. This article compares cotinine levels in dried blood spots to those in umbilical cord blood to assess cotinine in dried blood spots as a biomarker of maternal smoking close to the time of delivery. The California Genetic Disease Screening Program provided dried blood spots from 428 newborns delivered in 2001-2003 with known umbilical cord blood cotinine levels. Cotinine in dried blood spots was measured in 6.35--mm punches by using liquid chromatography--tandem mass spectrometry (quantitation limit, 3.1 ng/mL). Repeated measures of cotinine in dried blood spots were highly correlated (R(2) = 0.99, P < 0.001) among 100 dried blood spots with cotinine quantitated in 2 separate punches. Linear regression revealed that cotinine levels in dried blood spots were slightly lower than those in umbilical cord blood and predicted umbilical cord blood cotinine levels well (β = 0.95, R(2) = 0.80, and P < 0.001 for both cotinine levels in log10 scale). When defining active smoking as a cotinine level of 10 ng/mL or more and using umbilical cord blood cotinine as the criterion standard, we found that measurements of cotinine in dried blood spots had high sensitivity (92.3%) and specificity (99.7%) in the prediction of maternal active smoking. Cotinine levels in dried blood spots are an accurate biomarker of maternal smoking close to the time of delivery.
American journal of epidemiology 09/2013; 178(11). DOI:10.1093/aje/kwt182 · 5.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Smoking tobacco preparations in a water pipe (hookah) is widespread in many places of the world and is perceived by many as relatively safe. We investigated biomarkers of toxicant exposure with water pipe compared to cigarette smoking. Methods We conducted a cross-over study to assess daily nicotine and carcinogen exposure with water pipe and cigarette smoking in 13 people who were experienced in using both products. Results While smoking an average of 3 water pipe sessions compared to smoking 11 cigarettes per day, water pipe use was associated with a significantly lower intake of nicotine, greater exposure to carbon monoxide and a different pattern of carcinogen exposure compared to cigarette smoking, with greater exposure to benzene and high molecular weight PAHs, but less exposure to tobacco-specific nitrosamines, 1,3-butadiene and acrolein, acrylonitrile, propylene oxide, ethylene oxide, and low molecular weight PAHs. Conclusions A different pattern of carcinogen exposure might result in a different cancer risk profile between cigarette and water pipe smoking. Of particular concern is the risk of leukemia related to high levels of benzene exposure with water pipe use. Impact Smoking tobacco in water pipes has gained popularity in the United States and around the world. Many believe that water pipe smoking is not addictive and less harmful than cigarette smoking. We provide data on toxicant exposure that will help guide regulation and public education regarding water pipe health risk.
[Show abstract][Hide abstract] ABSTRACT: Measuring adherence to smoking cessation pharmacotherapy is important to evaluating its effectiveness. Blood levels are considered the most accurate measure of adherence but are invasive and costly. Pill counts and self-report are more practical, but little is known about their relationship to blood levels. This study compared the validity of pill count and self-report against plasma varenicline concentration for measuring pharmacotherapy adherence.
Data were obtained from a randomized pilot study of varenicline for smoking cessation among African American smokers. Adherence was measured on Day 12 via plasma varenicline concentration, pill count, 3-day recall, and a visual analogue scale (VAS; adherence was represented on a line with two extremes "no pills" and "all pills").
The sample consisted of 55 African American moderate to heavy smokers (average 16.8 cigarettes/day, SD = 5.6) and 63.6% were female. Significant correlations (p < .05) were found between plasma varenicline concentration and pill count (r = .56), 3-day recall (r = .46), and VAS (r = .29). Using plasma varenicline concentration of 2.0 ng/ml as the cutpoint for adherence, pill count demonstrated the largest area under the receiver operating characteristic curve (AUC = 0.85, p = .01) and had 88% sensitivity (95% CI = 75.0-95.0) and 80% specificity (95% CI = 30.0-99.0) for detecting adherence.
Of 3 commonly used adherence measures, pill count was the most valid for identifying adherence in this sample of African American smokers. Pill count has been used across other health domains and could be incorporated into treatment to identify nonadherence, which, in turn, could maximize smoking cessation pharmacotherapy use and improve abstinence rates.
[Show abstract][Hide abstract] ABSTRACT: Smoking tobacco preparations in a water pipe (hookah) is widespread in many places of the world, including the United States, where it is especially popular among young people. Many perceive water pipe smoking to be less hazardous than cigarette smoking. We studied systemic absorption of nicotine, carbon monoxide, and carcinogens from one water pipe smoking session.
Sixteen subjects smoked a water pipe on a clinical research ward. Expired carbon monoxide and carboxyhemoglobin were measured, plasma samples were analyzed for nicotine concentrations, and urine samples were analyzed for the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and polycyclic aromatic hydrocarbon (PAH) metabolite biomarker concentrations.
We found substantial increases in plasma nicotine concentrations, comparable to cigarette smoking, and increases in carbon monoxide levels that are much higher than those typically observed from cigarette smoking, as previously published. Urinary excretion of NNAL and PAH biomarkers increased significantly following water pipe smoking.
Absorption of nicotine in amounts comparable to cigarette smoking indicates a potential for addiction, and absorption of significant amounts of carcinogens raise concerns of cancer risk in people who smoke tobacco products in water pipes.
Our data contribute to an understanding of the health impact of water pipe use.
[Show abstract][Hide abstract] ABSTRACT: The nicotine metabolite cotinine is widely used to assess the extent of tobacco use in smokers, and secondhand smoke exposure in non-smokers. The ratio of another nicotine metabolite, trans-3'-hydroxycotinine, to cotinine in biofluids is highly correlated with the rate of nicotine metabolism, which is catalyzed mainly by cytochrome P450 2A6 (CYP2A6). Consequently, this nicotine metabolite ratio is being used to phenotype individuals for CYP2A6 activity and to individualize pharmacotherapies for tobacco addiction. In this paper we describe a highly sensitive liquid chromatography-tandem mass spectrometry method for determination of the nicotine metabolites cotinine and trans-3'-hydroxycotinine in human plasma, urine, and saliva. Lower limits of quantitation range from 0.02 to 0.1ng/mL. The extraction procedure is straightforward and suitable for large-scale studies. The method has been applied to several thousand biofluid samples for pharmacogenetic studies and for studies of exposure to low levels of secondhand smoke. Concentrations of both metabolites in urine of non-smokers with different levels of secondhand smoke exposure are presented.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 02/2011; 879(3-4):267-76. DOI:10.1016/j.jchromb.2010.12.012 · 2.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to analyse environmental tobacco smoke (ETS) and PAH metabolites in urine samples of non-occupationally exposed non-smoker adult subjects and to establish relationships between airborne exposures and urinary concentrations in order to (a) assess the suitability of the studied metabolites as biomarkers of PAH and ETS, (b) study the use of 3-ethenypyridine as ETS tracer and (c) link ETS scenarios with exposures to carcinogenic PAH and VOC. Urine samples from 100 subjects were collected and concentrations of monophenolic metabolites of naphthalene, fluorene, phenanthrene, and pyrene and the nicotine metabolites cotinine and trans-3'-hydroxycotinine were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess PAH and ETS exposures. Airborne exposures were measured using personal exposure samplers and analysed using GC-MS. These included 1,3-butadiene (BUT), 3-ethenylpyridine (3-EP) (a tobacco-specific tracer derived from nicotine pyrolysis) and PAHs. ETS was reported by the subjects in 30-min time-activity questionnaires and specific comments were collected in an ETS questionnaire each time ETS exposure occurred. The values of 3-EP (>0.25 microg/m(3) for ETS) were used to confirm the ETS exposure status of the subject. Concentrations as geometric mean, GM, and standard deviation (GSD) of personal exposures were 0.16 (5.50)microg/m(3) for 3-EP, 0.22 (4.28)microg/m(3) for BUT and 0.09 (3.03)ng/m(3) for benzo(a)pyrene. Concentrations of urinary metabolites were 0.44 (1.70)ng/mL for 1-hydroxypyrene and 0.88 (5.28)ng/mL for cotinine. Concentrations of urinary metabolites of nicotine were lower than in most previous studies, suggesting very low exposures in the ETS-exposed group. Nonetheless, concentrations were higher in the ETS population for cotinine, trans-3'hydroxycotinine, 3-EP, BUT and most high molecular weight PAH, whilst 2-hydroxyphenanthrene, 3+4-hydroxyphenanthrene and 1-hydroxyphenanthrene were only higher in the high-ETS subpopulation. There were not many significant correlations between either personal exposures to PAH and their urinary metabolites, or of the latter with ETS markers. However, it was found that the urinary log cotinine concentration showed significant correlation with log concentrations of 3-EP (R=0.75), BUT (R=0.47), and high molecular weight PAHs (MW>200), especially chrysene (R=0.55) at the p=0.01 level. On the other hand, low correlation was observed between the PAH metabolite 2-naphthol and the parent PAH, gas-phase naphthalene. These results suggest that (1) ETS is a significant source of inhalation exposure to the carcinogen 1,3-butadiene and high molecular weight PAHs, many of which are carcinogenic, and (2) that for lower molecular weight PAHs such as naphthalene, exposure by routes other than inhalation predominate, since metabolite levels correlated poorly with personal exposure air sampling.
Environment international 10/2010; 36(7):763-71. DOI:10.1016/j.envint.2010.05.015 · 5.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The association between tobacco smoke exposure and critical illness is not well studied, largely because obtaining an accurate smoking history from critically ill patients is difficult. Biomarkers can provide quantitative data on active and secondhand cigarette smoke exposure. We sought to compare cigarette smoke exposure as measured by biomarkers to exposure by self-report in a cohort of critically ill patients and to determine how well biomarkers of cigarette smoke exposure correlate with each other in this population.
Serum and urine cotinine and trans-3'-hydroxycotinine, urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, and hair and nail nicotine levels were measured in 60 subjects enrolled in an observational cohort of critically ill subjects at a tertiary academic medical center in Tennessee. Smoking history was obtained from patients, their surrogates, or the medical chart. Cigarette smoke exposure as measured by biomarkers was compared to exposure by history.
By smoking history, 29 subjects were identified as smokers, 28 were identified as nonsmokers, and 3 were identified as unknown. The combination of serum cotinine and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol identified 27 of the 28 nonsmokers by history either as active smokers (n = 6, 21%) or as exposed to secondhand smoke (n = 21, 75%). All biomarker levels were strongly correlated with each other (r = .69-.95, p < .0001).
The combination of serum cotinine and urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol identified considerably more active smokers than did smoking history and detected a high prevalence of secondhand smoke exposure in a critically ill population. These markers will be important for future studies investigating the relationship between active smoking and secondhand smoke exposure and critical illness.
Critical care medicine 10/2010; 39(1):40-5. DOI:10.1097/CCM.0b013e3181fa4196 · 6.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We sought to determine the optimal plasma and urine nicotine metabolites, alone or in combination, to estimate the systemic dose of nicotine after low-level exposure.
We dosed 36 nonsmokers with 100, 200, or 400 microg p.o. of deuterium-labeled nicotine (doses similar to exposure to secondhand smoke) daily for 5 days and then measured plasma and urine nicotine metabolites at various intervals over 24 hours.
The strongest correlations with nicotine dose were seen for the sum of four (cotinine+cotinine-glucuronide+trans-3'-hydroxycotinine+3HC-glucuronide) or six (including also nicotine+nicotine-glucuronide) of the major nicotine metabolites in 24-hour urine collection (r=0.96), with lesser correlations for these metabolites using spot urines corrected for creatinine at various times of day (r=0.72-0.80). The sum of plasma cotinine+trans-3'-hydroxycotine was more highly correlated with nicotine dose than plasma cotinine alone (r=0.82 versus 0.75).
Our results provide guidance for the selection of biomarkers to estimate the dose of nicotine taken in low-level (secondhand smoke) tobacco exposure.
This is probably relevant to active smoking as well.
[Show abstract][Hide abstract] ABSTRACT: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is tobacco specific and has a longer half-life than other tobacco biomarkers studied thus far. An accurate measurement of the NNAL half-life is important for optimal use to assess exposure to tobacco smoke. We determined the half-life of NNAL in urine in eight daily smokers on a clinical research ward and in five occasional smokers in a real-life environment. Total NNAL in urine was monitored for 14 days in daily smokers after stopping smoking and for up to 60 days in occasional smokers. The average half-life for the terminal phase in the daily smoker group using a two-compartmental body model was 10.3 days (beta phase), and using a noncompartmental model, it was 9.1 days. In the occasional group, these values were 17.6 and 16.0 days, respectively. The alpha-phase half-lives were 14.3 and 27.8 hours for the two groups, respectively. The inter-subject coefficient of variation of the NNAL terminal half-life ranged from 14% to 30%, and the intra-subject coefficient of variation ranged from 3% to 18%. There was very good agreement between the plasma and urinary half-lives in two subjects with plasma analyses: 7.4 versus 7.9 days and 9.2 versus 10.7 days. Mean renal clearance of NNAL was 13 +/- 2.3 mL/min. The terminal half-life of NNAL of 10 to 18 days indicates that this biomarker can be used to detect tobacco smoke exposure for 6 to 12 weeks after cessation of exposure and requires a similar time to assess the steady levels of NNAL after switching from one tobacco product to another.
[Show abstract][Hide abstract] ABSTRACT: Plasma or saliva cotinine concentrations are used widely as biomarkers of secondhand smoke (SHS) exposure and have been associated with the risk of SHS-related disease. Concentrations of cotinine and other nicotine metabolites are considerably higher in urine than in plasma or saliva, making chemical analysis easier. In addition, urine is often more convenient to collect in some SHS exposure studies. The optimal use of nicotine metabolites in urine, singly or in combination, with or without correction for urine creatinine concentration, to estimate plasma cotinine concentration with low-level nicotine exposure has not been determined.
We dosed 36 nonsmokers with 100, 200, or 400 microg deuterium-labeled nicotine (simulating exposure to SHS) by mouth daily for 5 days and then measured plasma and urine cotinine and metabolites at various intervals over 24 hr.
A plasma cotinine concentration of 1 ng/ml corresponds on average to a daily intake of 100 microg nicotine. Cotinine concentrations in urine averaged four to five times those in plasma. Correction of urine cotinine for creatinine concentration improved the correlation between urine and plasma cotinine. Measuring multiple cotinine metabolites in urine did not improve the correlation with plasma cotinine, compared with the use of urine cotinine alone.
Measurement of urine cotinine corrected for creatinine concentration appears to be the best predictor of plasma cotinine.
[Show abstract][Hide abstract] ABSTRACT: Exposure to secondhand tobacco smoke (SHS) has been linked to increased risk for a number of diseases, including lung cancer. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is of particular interest due to its potency and its specificity in producing lung tumors in animals. The NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine is frequently used as a biomarker for exposure. Due to its long half-life (40-45 days), NNAL may provide a long-term, time-averaged measure of exposure. We developed a highly sensitive liquid chromatography-tandem mass spectrometry method for determination of NNAL in human urine. The method involves liquid-liquid extraction followed by conversion to the hexanoate ester derivative. This derivative facilitates separation from interfering urinary constituents by extraction and chromatography and enhances detection with electrospray ionization mass spectrometry. The lower limit of quantitation is 0.25 pg/mL for 5-mL urine specimens. Applications to studies of people with a range of different SHS exposure levels is described.
[Show abstract][Hide abstract] ABSTRACT: Dietary supplements containing botanical forms of caffeine and ephedra alkaloids have been widely promoted and used in the U.S. for weight loss and athletic enhancement despite a lack of adequate research on the pharmacology of these botanical stimulants. In order to analyze dietary supplements and perform human pharmacokinetic studies, an analytical approach with good precision and accuracy was needed with sufficient sensitivity to detect very low levels of ephedra alkaloids. A liquid chromatography-atmospheric pressure chemical ionization (APCI) tandem mass spectrometry (LC-MS-MS) method was developed for quantitating the various ephedrine-group alkaloids found in dietary supplements that contain Ephedra species, and in plasma and urine of persons consuming these supplements. Using this method, low nanogram-per-milliliter concentrations of ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, methylephedrine, methylpseudoephedrine, and caffeine can be quantitated in a 12-min LC-MS-MS run.
[Show abstract][Hide abstract] ABSTRACT: In this study we determined urine concentration of the tobacco alkaloids anabasine and anatabine, nicotine and its metabolites cotinine, and nornicotine in 99 cigarette smokers and 205 smokeless tobacco users. We also investigated the possibility that anabasine and anatabine can be used as biomarkers for tobacco use during nicotine replacement therapy. Urine samples and data on self-reported tobacco use were obtained from subjects enrolled in tobacco cessation programs. Urine concentrations of tobacco alkaloids and metabolites were measured and correlated with self-reported tobacco use. Concentrations of anabasine and anatabine were used to validate abstinence in smokeless tobacco users who used nicotine gum as part of the therapy. Correlations of alkaloid concentration with self-reported tobacco use before treatment ranged from fair to poor. In subjects abstaining from smokeless tobacco but using nicotine gum, anabasine and anatabine levels were below the cut-point of 2 ng/ml despite high concentrations of nicotine and cotinine resulting from nicotine gum use. Anabasine and anatabine concentrations in urine can be used to validate abstinence or measure the extent of tobacco use in persons undergoing nicotine replacement therapy.
[Show abstract][Hide abstract] ABSTRACT: A major metabolite of norepinephrine (NE) in brain is 4-hydroxy-3-methoxyphenylethylene glycol (MHPG). In many species, a large fraction of MHPG formed in brain is converted to the sulfate conjugate. Consequently, MHPG sulfate has been proposed as a biomarker for NE metabolism in the central nervous system. As part of the clinical trials of the monoamine oxidase inhibitor selegiline for treating cocaine addiction, we required a method for measuring urine concentrations of MHPG sulfate. Using a deuterium-labeled analogue as an internal standard, we developed a liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/ MS) method for determination of MHPG sulfate in human urine. Sample preparation involves simply diluting 50 microL of urine with 1 mL of ammonium formate buffer and adding the internal standard. The sample is centrifuged, the supernate is transferred to an autosampler vial, and 10 microL is injected into the LC-MS/MS system. Standard curves from 50 to 10,000 ng/mL are generated. Only one sample of 277 clinical samples analyzed had a concentration outside of this range. Precision (coefficient of variation) ranged from 1.9 to 9.7%, and accuracy ranged from 97 to 103% of expected values for controls prepared by spiking sulfatase-treated urine with MHPG sulfate.
[Show abstract][Hide abstract] ABSTRACT: A major metabolite of norepinephrine (NE) in brain is 4-hydroxy-3-methoxyphenylethylene glycol (MHPG). In many species, a large fraction of MHPG formed in brain is converted to the sulfate conjugate. Consequently, MHPG sulfate has been proposed as a biomarker for NE metabolism in the central nervous system. As part of the clinical trials of the monoamine oxidase inhibitor selegiline for treating cocaine addiction, we required a method for measuring urine concentrations of MHPG sulfate. Using a deuterium-labeled analogue as an internal standard, we developed a liquid chromatography-electrospray ionization tandem mass spectrometry (LC-MS/ MS) method for determination of MHPG sulfate in human urine. Sample preparation involves simply diluting 50 muL of urine with 1 mL of ammonium formate buffer and adding the internal standard. The sample is centrifuged, the supernate is transferred to an autosampler vial, and 10 muL is injected into the LC-MS/MS system. Standard curves from 50 to 10 000 ng/mL are generated. Only one sample of 277 clinical samples analyzed had a concentration outside of this range. Precision (coefficient of variation) ranged from 1.9 to 9.7%, and accuracy ranged from 97 to 103% of expected values for controls prepared by spiking sulfatase-treated urine with MHPG sulfate.
[Show abstract][Hide abstract] ABSTRACT: The nicotine receptor antagonist mecamylamine has been shown to increase the efficacy of transdermal nicotine as a pharmacotherapy for tobacco addiction. A product for simultaneous transdermal administration of nicotine and mecamylamine is undergoing clinical trials. In order to carry out pharmacokinetic studies, quantitation of low nanogram per milliliter levels of mecamylamine and nicotine was required. This paper describes a method for simultaneous determination of mecamylamine, nicotine, and the nicotine metabolite, cotinine, in human plasma using gas chromatography-mass spectrometry (GC-MS). Limits of quantitation for mecamylamine, nicotine and cotinine are 2, 1 and 2 ng/ml, respectively.
Journal of Pharmaceutical and Biomedical Analysis 10/2000; 23(4):653-61. DOI:10.1016/S0731-7085(00)00343-5 · 2.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Menthol is widely used in a variety of commercial products and foods, but its clinical pharmacology is not well studied. To determine the disposition kinetics and to examine subjective and cardiovascular effects of menthol, we conducted a crossover placebo-controlled study that compared pure menthol versus placebo, along with an uncontrolled exposure to menthol in food or beverage. A novel assay for the measurement of menthol in biological fluids was also developed.Methods
Twelve subjects were studied; each received a 100 mg l-menthol capsule, a placebo capsule, and 10 mg menthol in mint candy or mint tea on three different occasions. Plasma and urine levels of menthol and conjugated menthol (glucuronide), cardiovascular measurements, and subjective effects were measured at frequent intervals.ResultsMenthol was rapidly metabolized, and only menthol glucuronide could be measured in plasma or urine. The plasma half-life of menthol glucuronide averaged 56.2 minutes (95% confidence interval [CI], 51.0 to 61.5) and 42.6 minutes (95% CI, 32.5 to 52.7) in menthol capsule and mint candy/mint tea conditions, respectively (P < .05). The plasma area under the plasma concentration-time curve ratios for menthol capsule to mint candy/mint tea treatment averaged 9.2 (95% CI, 8.2 to 10.1). Urinary recovery of menthol as the glucuronide averaged 45.6 and 56.6% for menthol capsule and mint candy/tea, respectively (difference not significant). After menthol capsule dosing, the decrease in heart rate was less than the decrease after placebo administration (P < .05). Menthol reduced subjective vigor value at 30 minutes.Conclusions
We conclude that pure menthol and menthol in food or beverages have a similar systemic bioavailability and that menthol has a small cardioaccelerating effect.Clinical Pharmacology & Therapeutics (1999) 66, 128-135; doi: 10.1053/cp.1999.v66.100455001
[Show abstract][Hide abstract] ABSTRACT: A selected ion monitoring method for determination of the tobacco alkaloids anabasine, anatabine, nornicotine, metanicotine, dihydrometanicotine, and 2,3'-bipyridyl in urine of smokers and smokeless tobacco users is described. The method involves conversion of the secondary amine alkaloids to tertiary amine derivatives by reductive alkylation using an aldehyde and sodium borohydride, and chromatography on a 5% phenylmethylsilicone capillary column. These derivatives have good chromatographic properties, allowing determination of concentrations as low as 1 ng/ml. The alkaloid 2,3'-bipyridyl is unaffected by the derivatization procedure and may be determined simultaneously with the other alkaloids. The structural analogues 2-(3-pyridyl)hexahydroazepine, 5-methyldihydrometanicotine, and 6-methyl-2,3'-bipyridyl were synthesized for use as internal standards. Using the method, concentrations and 24 h excretion of anabasine, anatabine, and nornicotine in urine of twenty-two smokers, eight chewing tobacco users, and six oral snuff users were determined and compared with concentrations and excretion of nicotine and its metabolite cotinine. Excretion of nicotine and cotinine was similar in all tobacco users, but excretion of anabasine, anatabine and nornicotine was substantially greater in urine of smokeless tobacco users, presumably due to absence of pyrolysis of these alkaloids in smokeless tobacco products.
Journal of Chromatography A 10/1993; 619(1):49-61. DOI:10.1016/0378-4347(93)80445-A · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A gas chromatographic method for the determination of the nicotine metabolite trans-3'-hydroxycotinine is described. The method involves conversion of the metabolite to the tert.-butyldimethylsilyl derivative, chromatography on a fused-silica capillary column, and determination using nitrogen-phosphorus detection or electron ionization mass spectrometry with selected ion monitoring. A structural analogue, trans-3-hydroxy-1-methyl-5-(2-pyridyl)pyrrolidin-2-one (trans-3'-hydroxy-ortho-cotinine), was used as an internal standard. Using selected ion monitoring, good precision and accuracy were obtained for determination of trans-3'-hydroxycotinine in urine over the concentration range 10-10,000 ng/ml. There was a good correlation between concentrations determined by selected ion monitoring and by nitrogen-phosphorus detection in urine of smokers, although low concentrations determined using nitrogen-phosphorus detection tended to be somewhat higher, suggesting some interference from urinary constituents. Concentrations and 24-h excretion of trans-3'-hydroxycotinine in the urine of 22 cigarette smokers are reported and compared to concentrations and excretion of nicotine, cotinine, nicotine 1'-N-oxide, nornicotine, and cotinine N-oxide.
Journal of Chromatography A 01/1993; 583(2):145-54. DOI:10.1016/0378-4347(92)80547-4 · 4.17 Impact Factor