Simultaneous determination of diquat and its two primary metabolites in rat plasma by ultraperformance liquid chromatography–tandem mass spectrometry and its application to the toxicokinetic study

PURPOSE: 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. METHOD: 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. RESULTS: 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(max)) was 977 ng/mL, half-life (t(1/2)) was 13.1 h, and area under the plasma concentration–time curve (AUC(0–t)) was 2770 h*ng/mL for DQ, C(max) was 47.1 ng/mL, t(1/2) was 25.1 h, and AUC(0–t) was 180 h·ng/mL for diquat monopyridone (DQ-M) and C(max) was 246 ng/mL, t(1/2) was 8.2 h, and AUC(0–t) was 2430 h·ng/mL for diquat dipyridone (DQ-D), respectively. CONCLUSIONS: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11419-022-00623-z.