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Determination of maternal and foetal distribution of cis- and trans-permethrin isomers and their metabolites in pregnant rats by liquid chromatography tandem mass spectrometry (LC-MS/MS)

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Abstract

We developed a method to quantify cis-permethrin and trans-permethrin and their metabolites in several biological matrices in pregnant rats and foetuses using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The objective was to quantify cis-permethrin and trans-permethrin in faeces, kidney, mammary gland, fat and placenta in mothers and in both maternal and foetal blood, brain and liver. The metabolites cis-3-(2,2-dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (cis-DCCA), trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (trans-DCCA) and 3-phenoxybenzoic acid (3-PBA) were measured in blood, liver and urine. Sample preparation was performed by liquid-liquid extraction. A purification step was not carried out except for the more complex biological samples (fat, mammary glands and faeces). Validation parameters including specificity, linearity, matrix effect, limits of quantification (LOQs), accuracy and precision were evaluated. The recoveries of target compounds ranged from 47 to 136%. LOQs were in the range 4 to 80 ng/mL for permethrin isomers and 4 to 800 ng/mL for their respective metabolites. Intra- and inter-batch precision and accuracy in matrix were better than 15%. The validated method was applied in a preliminary toxicokinetic study in pregnant rats with oral dosing of 50 mg/kg permethrin. In pregnant rats, permethrin isomers and their metabolites were quantified in all requested matrices except maternal liver and blood for trans-permethrin and cis-DCCA respectively. In foetuses, cis- and trans-permethrin were also quantified, demonstrating that the method is suitable for the analysis of foetal distribution of permethrin in toxicokinetic studies.

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Acknowledgements

This work was supported by the French Ministry of Ecology and Sustainable Development (Program 190). We would like to acknowledge Dr. Sophie Desmots for her help with the animal study.

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Correspondence to Florence Zeman.

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All experimental procedures were carried out in compliance with the Directive of the European Parliament and the Council (2010/63/UE) concerning the protection of animals used for scientific purpose [27] and approved by an internal ethics committee (C2EA-96).

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Personne, S., Marcelo, P., Pilard, S. et al. Determination of maternal and foetal distribution of cis- and trans-permethrin isomers and their metabolites in pregnant rats by liquid chromatography tandem mass spectrometry (LC-MS/MS). Anal Bioanal Chem 411, 8043–8052 (2019). https://doi.org/10.1007/s00216-019-02157-7

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