Development and validation of a sensitive and high throughput UPLC–MS/MS method for determination of paraquat and diquat in human plasma and urine: application to poisoning cases at emergency departments of hospitals

Paraquat and diquat are well-known toxic herbicides, at least responsible for hundreds of fatal poisoning events worldwide. However, the determination of diquat and paraquat in plasma and urine is very challenging because of their high polarity and double charge characteristics. In this study, we aim to develop a rapid and reliable method for the determination of paraquat and diquat in human plasma and urine by ultraperformance liquid chromatography–tandem mass spectrometry. The chromatographic separation of paraquat and diquat was tested with different chromatographic columns and different mobile phase conditions. The mass parameters were optimized by product ions, source gas flow, cone flow, desolvation temperature, and capillary voltage. The isocratic elution mode gave rapid appearance of peak of paraquat and diquat. The sharp peak shapes for paraquat and diquat were achieved with CORTECS® UPLC® HILIC (100 × 2.1 mm, 1.6 μm) column by adding formic acid and ammonium acetate in mobile phase in isocratic elution mode. The lower limit of quantification of 1.0 ng/mL for paraquat and diquat were achieved using only 50 μL of human plasma or urine. The running time for analysis of both paraquat and diquat was as short as 3.5 min per sample. A rapid and reliable method for the determination of paraquat and diquat was developed and applied to 387 clinical poisoning cases and 22 poisoning cases were found to be paraquat or diquat poisoning.