Department of Forensic Medicine, Nanjing Medical University, Nanjing, Jiangsu, 211166, People's Republic of China.
Department of Emergency, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Forensic Toxicol. 2022 Jul;40(2):332-339. doi: 10.1007/s11419-022-00623-z. Epub 2022 Apr 12.
This study aimed to develop and validate an ultraperformance liquid chromatography-tandem mass spectrometry to simultaneously determine diquat (DQ) and its two primary metabolites in rat plasma and its application to the toxicokinetic study.
The chromatographic separation of DQ and its two primary metabolites was performed with hydrophilic interaction chromatography column by adding formic acid and ammonium acetate in mobile phase in stepwise elution mode. DQ and its two primary metabolites were detected by liquid chromatography-tandem mass spectrometry in positive mode.
The lower limit of quantification ranging from 0.3 to 3.0 ng/mL for DQ and its two primary metabolites was achieved by using only 50 μL of rat plasma. The maximum concentration (C) was 977 ng/mL, half-life (t) was 13.1 h, and area under the plasma concentration-time curve (AUC) was 2770 h*ng/mL for DQ, C was 47.1 ng/mL, t was 25.1 h, and AUC was 180 h·ng/mL for diquat monopyridone (DQ-M) and C was 246 ng/mL, t was 8.2 h, and AUC was 2430 h·ng/mL for diquat dipyridone (DQ-D), respectively.
The validated method was shown to be suitable for simultaneous determination of diquat and its two primary metabolites in rat plasma. This study is the first to study the toxicokinetics of DQ and its two primary metabolites.
本研究旨在开发和验证一种超高效液相色谱-串联质谱法，用于同时测定大鼠血浆中的敌草快（DQ）及其两种主要代谢物，并将其应用于毒代动力学研究。
采用亲水作用色谱柱，通过在流动相中逐步洗脱的方式加入甲酸和乙酸铵，实现 DQ 及其两种主要代谢物的色谱分离。采用液相色谱-串联质谱法，在正离子模式下检测 DQ 及其两种主要代谢物。
仅使用 50 μL 大鼠血浆即可实现 DQ 及其两种主要代谢物的定量下限范围为 0.3 至 3.0 ng/mL。DQ 的最大浓度（C）为 977 ng/mL，半衰期（t）为 13.1 h，血浆浓度-时间曲线下面积（AUC）为 2770 h*ng/mL；DQ-M 的 C 为 47.1 ng/mL，t 为 25.1 h，AUC 为 180 h·ng/mL；DQ-D 的 C 为 246 ng/mL，t 为 8.2 h，AUC 为 2430 h·ng/mL。
该验证方法适用于同时测定大鼠血浆中的敌草快及其两种主要代谢物。本研究首次研究了 DQ 及其两种主要代谢物的毒代动力学。
