Determination of methyl-, 2-hydroxyethyl- and 2-cyanoethylmercapturic acids as biomarkers of exposure to alkylating agents in cigarette smoke

Scherer, Gerhard; Urban, Michael; Hagedorn, Hjalmar; Serafin, Richard; Feng, Shixia; Kapur, Sunil; Muhammad, Raheema; Jin, Yan; Sarkar, Mohamadi; Roethig, Hans‐Juergen

doi:10.1016/j.jchromb.2010.02.023

Cited by 28 publications

(17 citation statements)

References 23 publications

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“…The LLOQ for MHBMA and DHBMA were 0.5 and 4.4 ng/mL, respectively. 2-Hydroxyethylmercapturic acid (HEMA), a metabolite of ethylene oxide, and 2-cyanoethylmercapturic acid (CEMA), a metabolite of acrylonitrile had concentrations determined by liquid chromatography-tandem electrospray ionization (ESI, positive) mass spectroscopy (LC-MS/MS) according to Scherer et al (2010). Thiocyanate urinary concentrations were determined by a GC-MS method according to Riedel et al (2013), with a LLOQ of 0.7 lmol/L.…”

Section: Biomarker Analysismentioning

confidence: 99%

Consumption patterns and biomarkers of exposure in cigarette smokers switched to Snus, various dissolvable tobacco products, Dual use, or tobacco abstinence

Krautter

Chen

Borgerding

2015

Regulatory Toxicology and Pharmacology

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The objectives of this clinical study were to evaluate changes in tobacco product use behavior and levels of selected biomarkers of exposure (BOEs) for smokers who switched to one of six conditions during clinical confinement: exclusive use of; Camel Snus, Sticks, Strips or Orbs, controlled Dual use of cigarettes and Camel Snus, or tobacco abstinence. The controlled Dual use (DU) condition mandated a 60% reduction in cigarettes smoked per day (CPD). 167 healthy U.S. male and female smokers were randomized to the six groups (n=25-30/group). Subjects smoked their usual brand of cigarette for 1 day prior to switching to their designated intervention condition. Levels of thirty-two BOEs in plasma, whole blood, urine and feces were determined before and after switching. Questionnaires that scored nicotine dependence and withdrawal discomfort were also administered. After 5 days, exclusive Snus, Sticks, Strips, or Orbs use averaged 6.1, 5.9, 13.5, and 8.5 units/day, respectively. DU subjects smoked 7.6 CPD and used 3.2 Snus pouches/day, on average. After 5 days, substantial reductions of most biomarkers, including nicotine, were observed in all groups. Toxicant exposures were similar to being tobacco abstinent after switching exclusively to Camel Snus, Sticks, Strips or Orbs. DU reductions were more modest.

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Section: Biomarker Analysismentioning

confidence: 99%

Consumption patterns and biomarkers of exposure in cigarette smokers switched to Snus, various dissolvable tobacco products, Dual use, or tobacco abstinence

Krautter

Chen

Borgerding

2015

Regulatory Toxicology and Pharmacology

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“…The LOQ for MHBMA was improved to 0.1 ng/mL. Concentrations of 2-hydroxyethylmercapturic acid (HEMA), a metabolite of ethylene oxide, and 2-cyanoethylmercapturic acid (CEMA), a metabolite of acrylonitrile, were determined by LC-MS/MS according to SCHERER et al (37). Thiocyanate, a metabolite of hydrogen cyanide, was determined by GC-MS according to TORAÑO and VAN KAN (38), but employing a different internal standard: cyclohexyl bromide.…”

Section: Polycyclic Aromatic Hydrocarbonsmentioning

confidence: 99%

Changes in Biomarkers of Exposure and Subjective Effects When Smokers Switch to Dual Use of Cigarettes and Either Snus or a Dissolvable Tobacco Product: A Summary of Three Clinical Studies

Round

Campbell

Stiles

et al. 2015

Beiträge Zur Tabakforschung International/Contributions to Tobacco Research

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SUMMARYA series of ambulatory clinical studies were conducted to evaluate changes in biomarkers of tobacco exposure and subjective product ratings when adult smokers switched to dual use of cigarettes with Camel Strips (Strips), Camel Sticks (Sticks), or Camel (SNUS). In all studies, subjects smoked ad libitum for one week (baseline). In incremental stages over three subsequent weeks, subjects were instructed to reduce cigarettes per day (CPD) by at least 75% and include use of one type of smokeless tobacco product (STP). Product use data was recorded by subjects daily, questionnaires were administered and smoked cigarette filters and used snus pouches were collected weekly, and 24-hour urine samples were collected at baseline and the end of dual use for measurement of biomarkers of tobacco exposure. In total, 100 subjects were enrolled, and 88 completed the studies. At the end of dual use, mean CPD reductions of approximately 60% were reported in all studies. Median levels of biomarkers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and acrolein either did not statistically significantly change or showed statistically significant decreases in all studies. Serum and urinary nicotine biomarkers did not significantly change. Twentyfive additional biomarkers were measured only in the SNUS study. Of those, 18 biomarkers statistically significantly decreased 12.4-35.7%. No statistically significant increases in biomarker levels were observed in any of the studies. Decreases in some biomarkers confirmed that smoking reductions occurred but were less than the reported CPD reductions. Mouth-level exposure estimates suggest subjects did not significantly alter their puffing behavior to compensate for decreased CPD. Acceptability ratings of cigarettes decreased significantly during dual use, while ratings of Strips and SNUS increased, suggesting that the change in use behavior affected subjects' perceptions of the products. Results from these studies suggest that smokers who switch to dual use with either dissolvable tobacco or snus will likely not increase tobacco constituent exposure and may reduce exposure to some tobacco toxicants, especially those associated with combustion. [Beitr. Tabakforsch. Int. 26 (2015)

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“…Such VOCs can be determined either by directly measuring mainstream and environmental tobacco smoke (ETS) which, however, does not reflect the actual absorbed dose or by exposure assessment of appropriate biomarkers in different biofluids. VOCs are mainly determined in blood either directly as parent compounds [2][3][4] and DNA/protein adducts [5,6], or suitable metabolites are determined in urine [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Analysis of 18 urinary mercapturic acids by two high-throughput multiplex-LC-MS/MS methods

et al. 2015

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Mercapturic acids (MAs) are metabolic end products formed from conjugates between glutathione and electrophilic compounds. MAs are, therefore, suitable biomarkers of exposure to toxicants, which are either electrophiles by themselves or metabolized to electrophilic intermediates. We developed and validated two LC-MS/MS methods which allow the complementary, rapid, and sensitive determination of MAs derived from acrolein, acrylamide, acrylonitrile, benzene, 1,3-butadiene, crotonaldehyde, N,N-dimethylformamide, ethylene, ethylene oxide, vinyl chloride, propylene oxide, styrene, toluene as well as methylating and ethylating agents. Since separate determinations of single or small groups of MAs are time-consuming and expensive, we multiplexed several individual methods into two LC-MS/MS methods covering 18 individual mercapturic acids. Method validation according to FDA guidelines showed excellent results in terms of robustness, accuracy, and sensitivity of the methods. Moreover, the use of a minimal, simple, and straightforward sample cleanup procedure further accelerated the analytical workflow, which allows a time- and cost-efficient analysis of up to 18 MAs derived from various toxicants in environmental levels. The methods were applied to urine samples derived from a strictly diet-controlled clinical study, including 25 smoking and 25 non-smoking subjects. Significant increase in the urine concentrations in smokers as compared to non-smokers (p < 0.01; Student t test) was observed for 13 individual MAs. Moreover, a dose dependence was obtained for the majority of the analytes. In conclusion, the newly developed assays represent a powerful tool for the fast and reliable quantification of 18 MAs in clinical studies. A first method application suggests several suitable biomarkers for nine relevant toxicants in tobacco smoke.

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Determination of methyl-, 2-hydroxyethyl- and 2-cyanoethylmercapturic acids as biomarkers of exposure to alkylating agents in cigarette smoke

Cited by 28 publications

References 23 publications

Consumption patterns and biomarkers of exposure in cigarette smokers switched to Snus, various dissolvable tobacco products, Dual use, or tobacco abstinence

Consumption patterns and biomarkers of exposure in cigarette smokers switched to Snus, various dissolvable tobacco products, Dual use, or tobacco abstinence

Changes in Biomarkers of Exposure and Subjective Effects When Smokers Switch to Dual Use of Cigarettes and Either Snus or a Dissolvable Tobacco Product: A Summary of Three Clinical Studies

Analysis of 18 urinary mercapturic acids by two high-throughput multiplex-LC-MS/MS methods

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