色谱 ›› 2024, Vol. 42 ›› Issue (2): 185-193.DOI: 10.3724/SP.J.1123.2023.10022

• 研究论文 • 上一篇    下一篇

青少年体内35种抗生素和4种β-受体激动剂的测定及暴露现状分析

胡小键, 李振环, 谢琳娜, 付慧, 朱英()   

  1. 中国疾病预防控制中心环境与人群健康重点实验室, 中国疾病预防控制中心环境与健康相关产品安全所, 北京 100021
  • 收稿日期:2023-10-20 出版日期:2024-02-08 发布日期:2024-02-20
  • 通讯作者: * Tel:(010)50930161,E-mail:zhuying@nieh.chinacdc.cn.
  • 基金资助:
    中央财政经费项目(131031108000150003)

Determination of 35 antibiotics and four β-receptor agonists in teenagers and analysis of exposure status

HU Xiaojian, LI Zhenhuan, XIE Linna, FU Hui, ZHU Ying()   

  1. China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100021, China
  • Received:2023-10-20 Online:2024-02-08 Published:2024-02-20
  • Supported by:
    National Program for Central Financial Funds of China(131031108000150003)

摘要:

为了解我国青少年体内抗生素和β-受体激动剂的暴露水平,本研究采用同位素稀释-高通量全自动固相萃取-超高效液相色谱-串联质谱法测定某中学442名青少年(11~15岁)尿液中的7类共35种抗生素(5种大环内酯类、4种四环素类、10种喹诺酮类、3种β-内酰胺类、11种磺胺类、1种喹噁啉类和1种林可酰胺类)和4种β-受体激动剂的水平。尿样测定结果采用尿肌酐进行校正,所得到的样品检出率用于统计分析。采用皮尔森卡方检验对目标物检出率与性别、年龄和体重等级间的相关性进行分析。在调整了混杂因素后,采用Logistic回归模型来评估目标物检出率与不同组别间的相关性。分析结果发现,442名青少年中有397名青少年的尿液中检出抗生素或β-受体激动剂,总体检出率为89.8%。除喹噁啉类抗生素未被检出外,实验中共有6类27种抗生素和2种β-受体激动剂被检出,检出率为0.2%~59.0%;其中强力霉素、土霉素和阿奇霉素的检出率最高,检出率分别为59.0%、56.1%和34.6%;四环素类和大环内酯类抗生素是主要检出的两类抗生素,检出率分别为81.9%和42.3%;优先作为兽用的抗生素检出率最高(85.1%),其次为人用抗生素(41.0%), β-受体激动剂的总体检出率为2.7%。统计分析发现,四环素类抗生素在男性青少年尿液中的检出率高于女性,男性检出风险是女性的2.17倍。大环内酯类抗生素在不同年龄组间的检出率存在差异,与11岁青少年组相比,12、13岁青少年组的检出风险更高。实验发现,大环内酯类抗生素的检出率与青少年的肥胖程度呈正相关;在调整了年龄和性别因素后,肥胖青少年尿液中大环内酯类抗生素的检出风险是正常体重者的2.35倍。研究结果表明,青少年普遍暴露于低剂量的抗生素,且食物和环境中的抗生素可能是青少年体内抗生素暴露的主要来源,大环内酯类抗生素的暴露可能与青少年的肥胖风险相关。

关键词: 超高效液相色谱-串联质谱, 抗生素, β-受体激动剂, 青少年, 尿液, 暴露分析

Abstract:

Antibiotics are mainly used for disease treatment and prevention, and β-receptor agonists are mainly used in the clinical treatment of respiratory diseases. Both types of drugs are also widely used in animal husbandry and aquaculture to promote animal growth and prevent disease. These drugs enter the human body through many routes and cause harm to human health. Teenagers are in a critical period of growth and development, and long-term antibiotic exposure may have adverse effects on their bodies. In this study, 442 teenagers aged 11-15 years were recruited from a middle school to investigate the body burden of various antibiotics and β-receptor agonists. The seven categories of antibiotics, including five macrolides, four tetracyclines, 10 quinolones, 11 sulfonamides, three β-lactams, one quinoxaline, and one lincosamide, and four β-receptor agonists were determined by isotope dilution and solid phase extraction coupled with ultra performance liquid chromatography-tandem mass spectrometry. Analyte levels were corrected using urine creatinine, and detection rates were used for data analysis. Pearson’s chi-squared test was used to analyze the correlations between detection rate and gender, age, or body mass index (BMI). Logistic regression was used to evaluate the correlation between detection rate and different groups after adjusting for confounding factors. The results showed that 397 teenagers had at least one antibiotic or β-receptor agonist in their urine, with a total detection rate of 89.8%. A total of 29 antibiotics and β-receptor agonists were detected, and the detection rate of each compound ranged from 0.2% to 59.0%. Doxycycline, oxytetracycline, and azithromycin were the top three drugs with the highest detection rates (59.0%, 56.1%, and 34.6%, respectively). Tetracyclines and macrolides were the two antibiotic categories detected most often, with detection rates of 81.9% and 42.3%, respectively. Among the antibiotics investigated, preferred veterinary antibiotics (PVAs) had the highest detection rate (85.1%), followed by human antibiotics (HAs) (41.0%). The overall detection rate of β-receptor agonists was 2.7%. Statistical analysis showed that the male was prone to be exposed to tetracycline antibiotics (odds ratio (OR)=2.17). The detection rates of macrolides differed among the different age groups and were higher in those aged 12-13 years than in those aged 11 years. As the BMI of the teenagers increased, the detection rate of macrolides gradually increased. After adjusting for age and gender, teenagers with obesity were found to be 2.35 times more likely to be exposed to macrolides than those with a normal weight. The findings suggest that teenagers are generally exposed to low levels of antibiotics, that food and the environment may be the main sources of antibiotic exposure in teenagers, and that macrolide exposure may be associated with adolescent obesity.

Key words: ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), antibiotics, β-receptor agonists, teenagers, urine, exposure analysis

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