Quantitative analysis of nonsteroidal anti-inflammatory drugs in dried blood spot from mountain ultra-trail runners. Contribution of pharmacokinetic models for the interpretation of the results.

IF 2.6 3区 医学 Q2 BIOCHEMICAL RESEARCH METHODS
Mohammad Shafiq Mashal, Jérôme Guitton, Pierre Sallet, Laurent Bourguignon, Christelle Machon
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Abstract

Monitoring of drug use in athletes is of interest both for health and competition-related issues. Considering the advantages of Dried Blood Sampling (low invasiveness, easy sampling, long term storage), we have validated a quantitative LC-MS/HRMS method for the screening of 16 nonsteroidal anti-inflammatory drugs. For all drugs, accuracy and imprecision were within 15% for the 3 levels of quality control and lower than 20% for the lower limit of quantification. Application was performed from samples obtained for Ultra-Trail du Mont-Blanc® 2021 and 2022. A focus on ibuprofen and its metabolites (hydroxyibuprofen, carboxyibuprofen, ibuprofen glucuronide and hydroxyibuprofen glucuronide) was made because the results showed that it was the most detected nonsteroidal anti-inflammatory drug. Further, an interpretation of the ibuprofen concentrations was proposed either from experimental data obtained after an intake of ibuprofen by 10 control subjects, or from a pharmacokinetic modelling and simulations. Depending on the analytical performances of the method, we proposed possible detection windows for ibuprofen in runners. The pharmacokinetic model made it possible to consider two scenarios with and without modification of the total clearance of ibuprofen linked to a modification of the pharmacokinetics of the drugs due to the practice of a long and intense physical activity.

山地越野跑者干血斑中非甾体抗炎药物的定量分析。药代动力学模型对解读结果的贡献。
对运动员用药情况的监测既涉及健康问题,也涉及比赛相关问题。考虑到干血采样的优点(低侵入性、采样简便、可长期保存),我们验证了一种用于筛查 16 种非甾体类抗炎药物的 LC-MS/HRMS 定量方法。对于所有药物,3 级质控的准确度和不精确性均在 15%以内,定量下限低于 20%。对 2021 年和 2022 年 Ultra-Trail du Mont-Blanc® 采集的样本进行了应用。重点检测布洛芬及其代谢物(羟基布洛芬、羧基布洛芬、布洛芬葡萄糖醛酸苷和羟基布洛芬葡萄糖醛酸苷),因为结果显示布洛芬是检测出最多的非甾体抗炎药物。此外,还根据 10 名对照组受试者摄入布洛芬后获得的实验数据或药代动力学模型和模拟结果,对布洛芬的浓度进行了解释。根据该方法的分析性能,我们提出了跑步者布洛芬可能的检测窗口。通过药代动力学模型,我们可以考虑布洛芬总清除率发生改变和未发生改变的两种情况,这两种情况都与长时间剧烈运动导致的药代动力学改变有关。
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来源期刊
Drug Testing and Analysis
Drug Testing and Analysis BIOCHEMICAL RESEARCH METHODS-CHEMISTRY, ANALYTICAL
CiteScore
5.90
自引率
24.10%
发文量
191
审稿时长
2.3 months
期刊介绍: As the incidence of drugs escalates in 21st century living, their detection and analysis have become increasingly important. Sport, the workplace, crime investigation, homeland security, the pharmaceutical industry and the environment are just some of the high profile arenas in which analytical testing has provided an important investigative tool for uncovering the presence of extraneous substances. In addition to the usual publishing fare of primary research articles, case reports and letters, Drug Testing and Analysis offers a unique combination of; ‘How to’ material such as ‘Tutorials’ and ‘Reviews’, Speculative pieces (‘Commentaries’ and ‘Perspectives'', providing a broader scientific and social context to the aspects of analytical testing), ‘Annual banned substance reviews’ (delivering a critical evaluation of the methods used in the characterization of established and newly outlawed compounds). Rather than focus on the application of a single technique, Drug Testing and Analysis employs a unique multidisciplinary approach to the field of controversial compound determination. Papers discussing chromatography, mass spectrometry, immunological approaches, 1D/2D gel electrophoresis, to name just a few select methods, are welcomed where their application is related to any of the six key topics listed below.
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