一种用于人群暴露组全关联研究中血清化学混合物分析的新型靶向高通量工作流程
A novel targeted high-throughput workflow for serum chemical mixture profiling in population exposome-wide association studies.
A novel targeted high-throughput workflow for serum chemical mixture profiling in population exposome-wide association studies.
同时测定生物基质中组成复杂、酸解离常数范围宽泛的环境污染物是一项重大的分析挑战。本研究基于超高效液相色谱-串联质谱法(UHPLC-MS/MS)开发了一种高灵敏度、广谱的分析方法。通过采用磷脂去除净化(PRP)技术并优化流动相pH条件,我们实现了血清中230种环境污染物的同时定量。对样品前处理技术的比较评估表明,低温浓缩会导致防腐剂损失,而液-液萃取对多类化合物的回收率较差。PRP法因其在降低基质效应方面优于直接蛋白沉淀而被选为最优方法。方法验证表明,所有目标分析物均可准确定量(相对标准偏差,RSD<15.1%),98.3%的化合物回收率令人满意(80-120%)。对福清队列参与者血清样本的分析检测到22种检出频率>30%的污染物,其中PFHpA和PFOA被确定为高尿酸血症的危险因素。值得注意的是,我们首次提供了脱氢乙酸暴露与人群高尿酸血症患病率之间剂量-反应关系的证据。本研究为复杂生物样本中暴露组规模污染物的同时筛查建立了一种稳健的解决方案。
Simultaneous determination of environmental pollutants with complex compositions and wide-ranging acid dissociation constants in biological matrices presents a significant analytical challenge. This study developed a highly sensitive and broad-spectrum analytical method based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). By employing phospholipid removal purification (PRP) technology and optimizing mobile phase pH conditions, we achieved simultaneous quantification of 230 environmental pollutants in serum. Comparative evaluation of sample pretreatment techniques revealed that low-temperature concentration caused preservative loss, while liquid-liquid extraction showed poor recovery for multiple compound classes. The PRP method was selected as the optimal approach due to its superior performance in reducing matrix effects compared to direct protein precipitation. Method validation demonstrated accurate quantification of all target analytes (relative standard deviation, RSD <15.1%), with 98.3% of compounds exhibiting satisfactory recoveries (80-120%). Analysis of serum samples from the Fuqing cohort participants detected 22 contaminants with detection frequencies >30%, among which PFHpA and PFOA were identified as risk factors for hyperuricemia. Notably, we provide the first evidence of a dose-response relationship between dehydroacetic acid exposure and hyperuricemia prevalence in a human population. This study established a robust solution for simultaneous screening of exposome-scale pollutants in complex biological samples.
Yan Wu, Linlin Chen, Jie Zhang, Lisong Chen, Shanshan Du, Rui Ding, et al. A novel targeted high-throughput workflow for serum chemical mixture profiling in population exposome-wide association studies.. Talanta. 2027; doi:10.1016/j.talanta.2026.130275.
Yan Wu, Linlin Chen, Jie Zhang, Lisong Chen, Shanshan Du, Rui Ding, et al (2027). A novel targeted high-throughput workflow for serum chemical mixture profiling in population exposome-wide association studies.. Talanta. https://doi.org/10.1016/j.talanta.2026.130275
Yan Wu, Linlin Chen, Jie Zhang, Lisong Chen, Shanshan Du, Rui Ding, et al. A novel targeted high-throughput workflow for serum chemical mixture profiling in population exposome-wide association studies.[J]. Talanta, 2027 doi:10.1016/j.talanta.2026.130275.
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