A novel method for the quantification of the sulfur-containing metabolites of formaldehyde (thiazolidine carboxylic acid (TCA) and thiazolidine carbonyl glycine (TCG)) and acetaldehyde (methyl thiazolidine carboxylic acid (MTCA) and methyl thiazolidine carbonyl glycine (MTCG)) was developed and validated for human urine and plasma samples. Targeting the sulfur-containing metabolites of formaldehyde and acetaldehyde in contrast to the commonly used biomarkers formate and acetate overcomes the high intra- and inter-individual variance. Due to their involvement in various endogenous processes, formate and acetate lack the required specificity for assessing the exposure to formaldehyde and acetaldehyde, respectively. Validation was successfully performed according to FDA's Guideline for Bioanalytical Method Validation (2018), showing excellent performance with regard to accuracy, precision, and limits of quantification (LLOQ). TCA, TCG, and MTCG proved to be stable under all investigated conditions, whereas MTCA showed a depletion after 21 months. The method was applied to a set of pilot samples derived from smokers who consumed unfiltered cigarettes spiked with 13C-labeled propylene glycol and 13C-labeled glycerol. These compounds were used as potential precursors for the formation of 13C-formaldehyde and 13C-acetaldehyde during combustion. Plasma concentrations were significantly lower as compared to urine, suggesting urine as suitable matrix for a biomonitoring. A smoking-related increase of unlabeled biomarker concentrations could not be shown due to the ubiquitous distribution in the environment. While the metabolites of 13C-acetaldehyde were not detected, the described method allowed for the quantification of 13C-formaldehyde uptake from cigarette smoking by targeting the biomarkers 13C-TCA and 13C-TCG in urine.Graphical abstract.

中文翻译：

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一种用于人类尿液和血浆样品中甲醛和乙醛暴露的含硫生物标志物的新型定量方法。

建立了定量测定甲醛（噻唑烷羧酸（TCA）和噻唑烷羰基甘氨酸（TCG））和乙醛（甲基噻唑烷羧酸（MTCA）和甲基噻唑烷羰基甘氨酸（MTCG））的含硫代谢产物的新方法并已针对人类尿液和血浆样品进行了验证。与常用的生物标志物甲酸盐和乙酸盐相反，针对甲醛和乙醛的含硫代谢物克服了个体内和个体间的高差异。由于它们参与各种内源性过程，因此甲酸盐和乙酸盐缺乏分别评估甲醛和乙醛暴露所需的特异性。根据FDA的《生物分析方法验证指南》（2018）成功进行了验证，在准确性，精密度和定量限（LLOQ）方面显示出优异的性能。TCA，TCG和MTCG在所有研究条件下均证明是稳定的，而MTCA在21个月后显示衰竭。该方法适用于一组吸烟者的先导样品，这些吸烟者食用了掺有13C标记的丙二醇和13C标记的甘油的未过滤香烟。这些化合物被用作燃烧过程中形成13C-甲醛和13C-乙醛的潜在前体。与尿相比，血浆浓度显着降低，表明尿是生物监测的合适基质。由于环境中无处不在，因此未显示与吸烟相关的未标记生物标志物浓度的增加。虽然未检测到13C-乙醛的代谢物，