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超高效液相色谱-串联质谱法的开发与验证:同时定量测定有机磷农药的六种尿中二烷基磷酸酯代谢物

Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry Method Development and Validation to Quantify Simultaneously Six Urinary DIALKYL Phosphate Metabolites of Organophosphorus Pesticides.

作者信息

Đuc Ngo Kien, Khanh Truong Nhat, Thang Phan Nguyen Truong, Hung Tran Viet, Thu Pham Diem, Chi Le Thi Bich, Khuyen Vo Thi Kim, Tuan Nguyen Duc

机构信息

Faculty of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.

Institute of Drug Quality Control Ho Chi Minh City, Ho Chi Minh City, Vietnam.

出版信息

J Mass Spectrom. 2025 May;60(5):e5128. doi: 10.1002/jms.5128.

DOI:10.1002/jms.5128
PMID:40289302
Abstract

The exposure to chemical pesticides is one of the world's concerns, especially in Vietnam, which is becoming a key player in global agriculture. The chronic long-term exposure to pesticides, especially organophosphorus groups poses increased health risks such as cancer and related diseases due to their hazardous metabolites. The characterization of urinary pesticides is essential to understand the pesticide exposure patterns. Therefore, this research aims to develop a liquid chromatography-tandem mass spectrometry procedure for the quantification of six dialkyl phosphate metabolites of organophosphorus pesticides based on simulated human urine containing dialkyl phosphates and urine samples of organophosphorus pesticides-exposed farmers in An Giang province of Vietnam. As a result, a highly sensitive procedure with a negative ion atmospheric pressure chemical ionization source, fosfomycin as internal standard and multireaction monitoring, was successfully validated in compliance with international guidelines for simultaneous quantitative determination of six dialkyl phosphates in human urine samples. Molecular and fragmented ions for quantification were consistent with the standard spectrum. The linear ranges of DMP, DEP, DMTP, DETP, DMDTP, and DEDTP were 5.29-1000.58, 5.10-1000.19, 5.10-1000.20, 5.06-1000.11, 5.06-1000.11, 5.30-1000.60, and 5.06-1000.12 ng/mL, respectively. The validation results showed that the selectivity, intraday and interday precision and accuracy, matrix effect, carry over, dilution, and stability of all the analytes were in the acceptable range. In total, 383 spot urine samples from people working with pesticides were satisfactorily analyzed by the proposed procedure. Over 80% of farmers were detected with at least one organophosphate metabolite, especially DEDTP with high concentrations, up to 5015.0 ng/mL, which alerts the high likelihood of pesticide exposure in the community of rural areas in Vietnam.

摘要

接触化学农药是全球关注的问题之一,尤其是在越南,该国正成为全球农业的关键参与者。长期慢性接触农药,特别是有机磷类农药,由于其有害代谢物,会增加患癌症及相关疾病等健康风险。尿液中农药的特征分析对于了解农药接触模式至关重要。因此,本研究旨在基于含磷酸二烷基酯的模拟人尿和越南安江省接触有机磷农药的农民的尿液样本,开发一种液相色谱 - 串联质谱法,用于定量六种有机磷农药的磷酸二烷基酯代谢物。结果,采用负离子大气压化学电离源、以磷霉素作为内标并进行多反应监测的高灵敏度方法,成功按照国际指南进行了验证,可同时定量测定人尿样本中的六种磷酸二烷基酯。用于定量的分子离子和碎片离子与标准谱图一致。DMP、DEP、DMTP、DETP、DMDTP和DEDTP的线性范围分别为5.29 - 1000.58、5.10 - 1000.19、5.10 - 1000.20、5.06 - 1000.11、5.06 - 1000.11、5.30 - 1000.60和5.06 - 1000.12 ng/mL。验证结果表明,所有分析物的选择性、日内和日间精密度与准确度、基质效应、残留、稀释和稳定性均在可接受范围内。总共,所提出的方法对383份来自接触农药人员的即时尿样进行了令人满意的分析。超过80%的农民被检测出至少含有一种有机磷代谢物,尤其是DEDTP浓度很高,高达5015.0 ng/mL,这警示了越南农村地区社区农药接触的高可能性。

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