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首页> 外文会议>Annual conference of the International Society of Exposure Science >Rapid Determination of the Nonsteroidal Anti-inflammatory Drugs (NSAID) Paracetamol, Ibuprofen, Aspirin, Indomethacin and their Metabolites in Urine by On-line LC/LC-MS/MS
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Rapid Determination of the Nonsteroidal Anti-inflammatory Drugs (NSAID) Paracetamol, Ibuprofen, Aspirin, Indomethacin and their Metabolites in Urine by On-line LC/LC-MS/MS

机译：在线LC / LC-MS / MS快速测定尿液中的非甾体抗炎药（扑热息痛），扑热息痛，布洛芬，阿司匹林，吲哚美辛及其代谢物

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Paracetamol (acetaminophen), ibuprofen and aspirin are heavily sold over-the-counter analgesics and anti-pyretic drugs and are commonly used for self-treatment of several afflictions. Indomethacin is a prescription medication for symptomatic therapy of rheumatic diseases. Especially paracetamol is often used during pregnancy. Recent association studies suggest increased reproductive disorders in males after prenatal exposure to these substances in the past. Despite the widespread use of these substances and the suggested endocrine disrupting effects there is limited exposure data available based upon human biomonitoring measurements. We expanded our recently developed online LC-MS/MS method for the determination of paracetamol in human urine to include aspirin, ibuprofen and indomethacin as well as selected metabolites including paracetamol-3-mercapturate, salicyluric acid and 2-hydroxyibuprofen. After enzymatic hydrolysis of their glucuronide conjugates, target analytes were extracted from urine and enriched with turbulent flow chromatography on a Waters Oasis ® HLB column. Final chromatographic separation was carried out on a Thermo AccucoreTM Phenyl-X column followed by sensitive tandem mass spectrometric detection. Isotope-labelled internal standards were used for quantification. We achieved limits of quantification of 1 -5μg/L depending on the analyte, thus sufficiently low to detect both possible background exposures (as we already described for paracetamol) and medically indicated treatments. The latter can result in urinary levels in the mg/L or g/L range. We will provide first human biomonitoring data on these analgesics both for users and the general population. This method can be used in the future in population studies to (retrospectively) classify NSAID users and NSAID consumption in the general population or potentially susceptible subsets like pregnant women or children.
机译：扑热息痛（对乙酰氨基酚），布洛芬和阿司匹林是大量出售的非处方镇痛药和退热药，通常用于几种疾病的自我治疗。消炎痛是风湿性疾病对症治疗的处方药。特别是在怀孕期间经常使用扑热息痛。最近的关联研究表明，过去在产前接触这些物质后，男性生殖功能异常增加。尽管这些物质的广泛使用和建议的内分泌干扰作用，但基于人体生物监测测量的可用暴露数据有限。我们扩展了我们最近开发的在线LC-MS / MS方法，用于测定人尿中对乙酰氨基酚，包括阿司匹林，布洛芬和吲哚美辛，以及选定的代谢物，包括对乙酰氨基酚3-巯基乙酸，水杨酸和2-羟基布洛芬。将其葡糖醛酸苷结合物酶水解后，从尿液中提取目标分析物，并在WatersOasis®HLB色谱柱上进行湍流色谱法富集。在Thermo AccucoreTM Phenyl-X色谱柱上进行最终色谱分离，然后进行灵敏的串联质谱检测。同位素标记的内标用于定量。根据分析物的不同，我们达到了1-5μg/ L的定量限，因此足够低，无法检测可能的背景暴露（如我们已经描述过的扑热息痛）和医学上指定的治疗方法。后者可导致尿液浓度在mg / L或g / L范围内。我们将为用户和一般人群提供有关这些止痛剂的首个人类生物监测数据。将来，该方法可用于人群研究，以（回顾性）对一般人群或潜在易感人群（如孕妇或儿童）中的NSAID使用者和NSAID消耗量进行分类。

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