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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

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Abstract

Purpose

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.

Method

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.

Results

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.

Conclusions

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.

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References

  1. Monte AA, Sun H, Rapp-Olsson AM, Mohamed F, Gawarammana I, Buckley NA, Evans CM, Yang IV, Schwartz DA (2018) The plasma concentration of MUC5B is associated with clinical outcomes in paraquat-poisoned patients. Am J Respir Crit Care Med 197:663–665. https://doi.org/10.1164/rccm.201705-0866LE (open access article)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wunnapuk K, Mohammed F, Gawarammana I, Liu X, Verbeeck RK, Buckley NA, Roberts MS, Musuamba FT (2014) Prediction of paraquat exposure and toxicity in clinically ill poisoned patients: a model based approach. Br J Clin Pharmacol 78:855–866. https://doi.org/10.1111/bcp.12389 (open access article)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Magalhães N, Carvalho F, Dinis-Oliveira RJ (2018) Human and experimental toxicology of diquat poisoning: toxicokinetics, mechanisms of toxicity, clinical features, and treatment. Hum Exp Toxicol 37:1131–1160. https://doi.org/10.1177/0960327118765330

    Article  CAS  PubMed  Google Scholar 

  4. Pizzutti IR, Vela GME, de Kok A, Scholten JM, Dias JV, Cardoso CD, Concenço G, Vivian R (2016) Determination of paraquat and diquat: LC–MS method optimization and validation. Food Chem 209:248–255. https://doi.org/10.1016/j.foodchem.2016.04.069

    Article  CAS  PubMed  Google Scholar 

  5. Oulkar D, Shinde R, Khan Z, Banerjee K (2019) High throughput residue analysis of paraquat and diquat involving hydrophilic interaction liquid chromatographic separation and mass spectrometric determination. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 36:120–130. https://doi.org/10.1080/19440049.2018.1547424

    Article  CAS  PubMed  Google Scholar 

  6. Hao C, Zhao X, Morse D, Yang P, Taguchi V, Morra F (2013) Optimized liquid chromatography tandem mass spectrometry approach for the determination of diquat and paraquat herbicides. J Chromatogr A 1304:169–176. https://doi.org/10.1016/j.chroma.2013.07.033

    Article  CAS  PubMed  Google Scholar 

  7. Ariffin MM, Anderson RA (2006) LC/MS/MS analysis of quaternary ammonium drugs and herbicides in whole blood. J Chromatogr B 842:91–97. https://doi.org/10.1016/j.jchromb.2006.03.051

    Article  CAS  Google Scholar 

  8. Ruan X-L, Qiu J-J, Wu C, Huang T, Meng R-B, Lai Y-Q (2014) Magnetic single-walled carbon nanotubes-dispersive solid-phase extraction method combined with liquid chromatography-tandem mass spectrometry for the determination of paraquat in urine. J Chromatogr B 965:85–90. https://doi.org/10.1016/j.jchromb.2014.06.016

    Article  CAS  Google Scholar 

  9. Wunnapuk K, Medley GA, Liu X, Grice JE, Jayasinghe S, Gawarammana I, Buckley NA, Roberts MS (2011) Simple and sensitive liquid chromatography-tandem mass spectrometry methods for quantification of paraquat in plasma and urine: application to experimental and clinical toxicological studies. J Chromatogr B 879:3047–3052. https://doi.org/10.1016/j.jchromb.2011.09.008

    Article  CAS  Google Scholar 

  10. European Medicines Agency (2015) Guideline on bioanalytical method validation, London. https://www.ema.europa.eu/en/documents/scientific–guideline/guideline–bioanalytical–method–validation_en.pdf. Accessed 3 Jun 2015

  11. Food and Drug Administration, USA (2018) Bioanalytical method validation guidance for industry. http://www.fda.gov/files/drugs/published/Bioanalytical–Method–Validation–Guidance–for–Industry.pdf. Accessed 24 May 2018

  12. Lee X-P, Kumazawa T, Fujishiro M, Hasegawa C, Arinobu T, Seno H, Ishii A, Sato K (2004) Determination of paraquat and diquat in human body fluids by high-performance liquid chromatography/tandem mass spectrometry. J Mass Spectrom 39:1147–1152. https://doi.org/10.1002/jms.695

    Article  CAS  PubMed  Google Scholar 

  13. Whitehead RD Jr, Montesano MA, Jayatilaka NK, Buckley B, Winnik B, Needham LL, Barr DB (2009) Method for measurement of the quaternary amine compounds paraquat and diquat in human urine using high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr B 878:2548–2553. https://doi.org/10.1016/j.jchromb.2009.09.029

    Article  CAS  Google Scholar 

  14. Yoshioka N, Asano M, Kuse A, Matsuoka T, Akiyama Y, Mitsuhashi T, Nagasaki Y, Ueno Y (2012) Rapid and sensitive quantification of paraquat and diquat in human serum by liquid chromatography/time-of-flight mass spectrometry using atmospheric pressure photoionization. Forensic Toxicol 30:135–141. https://doi.org/10.1007/s11419-012-0138-5

    Article  CAS  Google Scholar 

  15. Tsao Y-C, Lai Y-C, Liu H-C, Liu R-H, Lin D-L (2016) Simultaneous determination and quantitation of paraquat, diquat, glufosinate and glyphosate in postmortem blood and urine by LC–MS–MS. J Anal Toxicol 40:427–436. https://doi.org/10.1093/jat/bkw042 (open access article)

    Article  CAS  PubMed  Google Scholar 

  16. Suzuki Y, Kaneko T, Saito K (2018) The internal standard diquat-d4 causes errors in diquat analysis by LC–MS/MS. Forensic Toxicol 36:458–466. https://doi.org/10.1007/s11419-018-0423-z

    Article  CAS  Google Scholar 

  17. Lu H, Yu J, Wu L, Xing J, Wang J, Huang P, Zhang J, Xiao H, Gao R (2016) Optimized ultra performance liquid chromatography tandem high resolution mass spectrometry method for the quantification of paraquat in plasma and urine. J Chromatogr B 1027:96–102. https://doi.org/10.1016/j.jchromb.2016.05.030

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by the Natural Science Research of Jiangsu Higher Education Institutions of China (Grant No. 20KJB340001) and the National Natural Science Foundation of China (Grant No. 82002028).

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Correspondence to Zhengsheng Mao or Feng Chen.

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This study was approved by the ethics committee of the Nanjing Medical University.

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Mao, Z., Yu, Y., Sun, H. et al. 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. Forensic Toxicol 40, 102–110 (2022). https://doi.org/10.1007/s11419-021-00603-9

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  • DOI: https://doi.org/10.1007/s11419-021-00603-9

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