健康人血清四环素、磺胺类抗生素水平及内暴露概率评估

Levels of serum tetracycline and sulfonamide antibiotics and assessment on internal exposure probability in healthy human

目的运用高效液相色谱-串联质谱联用(LC-MS/MS)方法检测健康人血清四环素、磺胺类抗生素水平,运用Monte Carlo概率模拟方法评估人群抗生素内暴露水平,为其潜在风险的防控提供依据。方法收集2020年11月至12月,申请公共服务行业就业前健康检查人员的血清样本33例,经预处理后以LC-MS/MS法检测抗生素的含量,以Oracle Crystal ball软件行Monte Carlo概率模拟评估人群抗生素内暴露水平。结果在11种目标抗生素中,共有6种被检出,检出率高低依次为金霉素(CTC)>磺胺甲噻二唑(STZ)>磺胺甲恶唑(SMZ)>四环素(TC)>强力霉素(DOX)>土霉素(OTC),检出率无性别差异(P>0.05),未见不同抗生素之间存在Spearman相关及检出率Kappa分析一致性。此外,Crystal ball概率模拟符合条件的5种抗生素结果表明,人群内暴露水平服从Logistic、Min Extreme、Beta等不同分布类型,50%及95%个体的内暴露水平分别为CTC(1.71和4.22 g/mL),DOX(0.21和1.25 g/mL),TC(1.64和3.51 g/mL),STZ(0.88和1.76 g/mL),SMZ(0.50和1.00 g/mL)等。结论非医源性暴露抗生素的潜在危害不容忽视,契合人群多途径、多组分抗生素共同暴露特点的等效性研究有望成为新的研究热点。

Objective To monitor the levels of tetracycline and sulfa antibiotics in serum of healthy population by LC-MS/MS method and evaluate the internal exposure probability of antibiotics by Monte Carlo probability,so as to provide references for their potential risk control.Methods A total of 33 serum samples were collected by volunteer who applied for pre-employment health check-ups from November to December 2020.After sample pre-treatment,antibiotic concentration in serum was detected by LC-MS/MS method and internal exposure probability of antibiotics were evaluated by using Monte Carlo probability simulation.Results Six out of eleven target antibiotics were detected,with the descending order of detection rate was chlortetracycline(CTC)>sulfamethizole(STZ)>sulfamethoxazole(SMZ)>tetracycline(TC)>Doxycycline(DOX)>oxytetracycline(OTC),with no gender difference in the detection rate(P>0.05).There was no Spearman correlation among antibiotics and no Kappa analysis consistency in the detection rate.Probabilistic simulation revealed the antibiotics internal exposure comformed to Logistic,Min Extreme,Beta distribution respectively.The 50%and 95%of individual exposure dose were CTC(1.71,4.22 g/mL),DOX(0.21,1.25 g/mL),TC(1.64,3.51 g/mL),STZ(0.88,1.76 g/mL),SMZ(0.50,1.00 g/mL).Conclusion The potential hazards of non-iatrogenic exposure to antibiotics cannot be ignored and equivalence research are expected to be a new research hotspot for corresponding to multi-channel and multi-component antibiotic co-exposure characteristics in population.