BASF SE, Corporate Health Management, Ludwigshafen, Germany.
Anal Methods. 2020 Dec 21;12(47):5718-5728. doi: 10.1039/d0ay01582b. Epub 2020 Nov 21.
Geraniol is a fragrance which occurs in natural terpene oil or is chemically synthesized on a large scale. It is used in a wide variety of consumer products such as perfumes, deodorants, household products and cosmetics. Hence, not only industry workers in the production of geraniol, but also consumers can come into contact with the substance. Human biomonitoring (HBM), i.e. the analytical determination of substances and their metabolites in human biological material, is a key element in the analysis and assessment of the distribution and intensity of occupational and environmental exposure of humans. Therefore, a procedure for the quantitative determination of the urinary metabolites Hildebrandt acid, geranic acid, 3-hydroxycitronellic acid and 8-carboxygeraniol as potential biomarkers of geraniol exposure was developed and validated. The method is based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after enzymatic hydrolysis and liquid-liquid extraction (LLE) of the target analytes. The limit of quantification (LOQ) is 1.5 μg L for 8-carboxygeraniol, 2.7 μg L each for Hildebrandt acid and geranic acid, and 1.8 μg L for 3-hydroxycitronellic acid. The method was applied to urine samples of 41 persons without occupational exposure to geraniol. Hildebrandt acid and geranic acid were detected in all samples, 8-carboxygeraniol in 83% and 3-hydroxycitronellic acid in 81% of the samples. Hildebrandt acid (median: 313 μg L, range: 37-1966 μg L) was the most abundant metabolite, followed by geranic acid (93 μg L; 9-477 μg L), 3-hydroxycitronellic acid (18 μg L; <LOQ to 70 μg L) and 8-carboxygeraniol (9 μg L; <LOQ to 46 μg L). Hildebrandt acid, geranic acid and 3-hydroxycitronellic acid apparently represent larger relative fractions of the eliminated metabolites, but they are not strictly specific for geraniol since they are metabolites of other terpenes as well, such as citral. In contrast, geraniol seems to be the only parent compound for 8-carboxygeraniol, which makes this metabolite a promising candidate for specific human biomonitoring and risk assessment.
香叶醇是一种天然萜烯油中存在的香气成分，或通过大规模化学合成得到。它被广泛应用于各种消费品中，如香水、除臭剂、家用产品和化妆品。因此，不仅是香叶醇生产行业的工人，还有消费者都可能接触到这种物质。人体生物监测（HBM），即分析人类生物材料中物质及其代谢物的含量，是分析和评估人类职业和环境暴露分布和强度的关键要素。因此，开发并验证了一种用于定量测定尿代谢产物胡椒酸、香叶酸、3-羟基香茅酸和 8-羧基香叶醇作为香叶醇暴露的潜在生物标志物的方法。该方法基于超高效液相色谱-串联质谱法（UPLC-MS/MS），在目标分析物经酶解和液液萃取（LLE）后进行分析。8-羧基香叶醇的定量限（LOQ）为 1.5μg/L，胡椒酸和香叶酸各为 2.7μg/L，3-羟基香茅酸为 1.8μg/L。该方法应用于 41 名无职业性香叶醇接触史的人的尿液样本。所有样本中均检测到胡椒酸和香叶酸，83%的样本中检测到 8-羧基香叶醇，81%的样本中检测到 3-羟基香茅酸。胡椒酸（中位数：313μg/L，范围：37-1966μg/L）是最丰富的代谢物，其次是香叶酸（93μg/L；9-477μg/L）、3-羟基香茅酸（18μg/L；<LOQ 至 70μg/L）和 8-羧基香叶醇（9μg/L；<LOQ 至 46μg/L）。胡椒酸、香叶酸和 3-羟基香茅酸显然代表了排泄代谢物中更大的相对比例，但它们并不严格特异于香叶醇，因为它们也是其他萜烯的代谢物，如柠檬醛。相比之下，香叶醇似乎是 8-羧基香叶醇的唯一母体化合物，这使得该代谢物成为特定的人体生物监测和风险评估的有前途的候选物。
