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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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Smoking conventional lit-end cigarettes results in exposure of nonsmokers to potentially harmful cigarette smoke constituents present in environmental tobacco smoke (ETS) generated by sidestream smoke emissions and exhaled mainstream smoke. ETS constituent concentrations generated by a conventional lit-end cigarette and a newly developed electrically heated cigarette smoking system (EHCSS) that produces only mainstream smoke and no sidestream smoke emissions were investigated in simulated "office" and "hospitality" environments with different levels of baseline indoor air quality. Smoking the EHCSS (International Organisation for Standardization yields: 5 mg tar, 0.3 mg nicotine, and 0.6 mg carbon monoxide) in simulated indoor environments resulted in significant reductions in ETS constituent concentrations compared to when smoking a representative lit-end cigarette (Marlboro: 6 mg tar, 0.5 mg nicotine, and 7 mg carbon monoxide). In direct comparisons, 24 of 29 measured smoke constituents (83%) showed mean reductions of greater than 90%, and 5 smoke constituents (17%) showed mean reductions between 80% and 90%. Gas-vapor phase ETS markers (nicotine and 3-ethenylpyridine) were reduced by an average of 97% (range 94-99%). Total respirable suspended particles, determined by online particle measurements and as gravimetric respirable suspended particles, were reduced by 90% (range 82-100%). The mean and standard deviation of the reduction of all constituents was 94 ± 4%, indicating that smoking the new EHCSS in simulated "office" and "hospitality" indoor environments resulted in substantial reductions of ETS constituents in indoor air.

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2-(4-tert-Butylbenzyl)propionaldehyde also known as lysmeral, lilial, or lily aldehyde (CAS No. 80-54-6) is a synthetic odorant mainly used as a fragrance in a variety of consumer products like cleaning agents, fine fragrances, cosmetics, and air fresheners. Due to its broad application in various fields, lysmeral was selected for the development of a biomonitoring method for the quantitative exposure assessment within the frame of the cooperation project of the Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB) and the German Chemical Industry Association (VCI). A method based on ultra-high pressure liquid chromatography combined with tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous determination of potential biomarkers of lysmeral in human urine samples. Sample cleanup was performed by liquid-liquid extraction (LLE). Quantification was achieved by standard addition using stable isotope-labeled, authentic reference standards. The method is characterized by its robustness, reliability, and excellent sensitivity as proven during method validation according to approved standard guidelines. The following five lysmeral metabolites were identified as potential biomarkers of exposure for lysmeral in human urine samples: lysmerol, lysmerylic acid, hydroxylated lysmerylic acid, tert-butylbenzoic acid (TBBA), and tert-butylhippuric acid (TBHA). The determination of lysmerol required derivatization with 3-nitrophthalic acid anhydride and showed the lowest limit of detection (LOD) and limit of quantification (LOQ) in urine (0.035 and 0.10 μg/L, respectively). LOD and LOQ for the other metabolites were in the range of 0.12-0.15 and 0.36-0.45 μg/L, respectively. Accuracy for all analytes was in the range of 90-110 %. Intra- and inter-day precision was in the range of 5-10 %, except for TBHA, for which the coefficient of variation was unacceptably high (>20 %) and therefore excluded from the method. The method was applied to urine samples of 40 adult volunteers. The four remaining lysmeral metabolites were detectable in most of the 40 urine samples in the following order according to quantity excreted: TBBA >> lysmerol ≈ lysmerylic acid > hydroxy-lysmerylic acid. In conclusion, we successfully developed a biomonitoring method for the assessment of the exposure to lysmeral in the general population. The method is characterized by its precision, robustness, and accuracy. The metabolites lysmerol, lysmerylic acid, hydroxylated lysmerylic acid, and TBBA turned out to be suitable biomarkers of exposure to lysmeral, either alone or in combination with one or more of the other metabolites. Sensitivity was found to be sufficient for assessing the background exposure to this chemical in the general population.

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