Skip to main content
Log in

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)

Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript


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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6


  1. Saillenfait A-M, Ndiaye D, Sabaté J-P. Pyrethroids: exposure and health effects – an update. Int J Hyg Environ Health. 2015;218:281–92.

    Article  CAS  PubMed  Google Scholar 

  2. Heudorf U, Angerer J. Metabolites of pyrethroid insecticides in urine specimens: current exposure in an urban population in Germany. Environ Health Perspect. 2001;109:213.

    Article  CAS  Google Scholar 

  3. Barr DB, Olsson AO, Wong L-Y, Udunka S, Baker SE, Whitehead RD, et al. Urinary concentrations of metabolites of pyrethroid insecticides in the general U.S. population: National Health and Nutrition Examination Survey 1999–2002. Environ Health Perspect. 2010;118:742–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dereumeaux C, Fillol C, Charles M-A, Denys S. The French human biomonitoring program: first lessons from the perinatal component and future needs. Int J Hyg Environ Health. 2017;220:64–70.

    Article  PubMed  Google Scholar 

  5. Soderlund DM. Molecular mechanisms of pyrethroid insecticide neurotoxicity: recent advances. Arch Toxicol. 2012;86:165–81.

    Article  CAS  PubMed  Google Scholar 

  6. Shafer TJ, Meyer DA, Crofton KM. Developmental neurotoxicity of pyrethroid insecticides: critical review and future research needs. Environ Health Perspect. 2004;113:123–36.

    Article  CAS  PubMed Central  Google Scholar 

  7. Horton MK, Rundle A, Camann DE, Boyd Barr D, Rauh VA, Whyatt RM. Impact of prenatal exposure to piperonyl butoxide and permethrin on 36-month neurodevelopment. PEDIATRICS. 2011;127:e699–706.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Shelton JF, Geraghty EM, Tancredi DJ, Delwiche LD, Schmidt RJ, Ritz B, et al. Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: the CHARGE study. Environ Health Perspect. 2014.

  9. Fluegge KR, Nishioka M, Wilkins JR III. Effects of simultaneous prenatal exposures to organophosphate and synthetic pyrethroid insecticides on infant neurodevelopment at three months of age. J Environ Toxicol Public Health. 2016;1:60.

    PubMed  PubMed Central  Google Scholar 

  10. Hisada A, Yoshinaga J, Zhang J, Kato T, Shiraishi H, Shimodaira K, et al. Maternal exposure to pyrethroid insecticides during pregnancy and infant development at 18 months of age. Int J Environ Res Public Health. 2017;14:52.

    Article  CAS  PubMed Central  Google Scholar 

  11. Richardson JR, Taylor MM, Shalat SL, Guillot TS, Caudle WM, Hossain MM, et al. Developmental pesticide exposure reproduces features of attention deficit hyperactivity disorder. FASEB J. 2015;29:1960–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. US EPA. Pesticides industry sales and usage 2008-2012. Market estimates. 2016.

  13. Stout DM II, Bradham KD, Egeghy PP, Jones PA, Croghan CW, Ashley PA, et al. American Healthy Homes Survey: a national study of residential pesticides measured from floor wipes. Environ Sci Technol. 2009;43:4294–300.

    Article  CAS  PubMed  Google Scholar 

  14. Starr JM, Scollon EJ, Hughes MF, Ross DG, Graham SE, Crofton KM, et al. Environmentally relevant mixtures in cumulative assessments: an acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids. Toxicol Sci. 2012;130:309–18.

    Article  CAS  PubMed  Google Scholar 

  15. Yan X, Lashley S, Smulian JC, Ananth CV, Barr DB, Ledoux TA, et al. Pesticide concentrations in matrices collected in the perinatal period in a population of pregnant women and newborns in New Jersey, USA. Hum Ecol Risk Assess Int J. 2009;15:948–67.

    Article  CAS  Google Scholar 

  16. Willemin M-E, Desmots S, Le Grand R, Lestremau F, Zeman FA, Leclerc E, et al. PBPK modeling of the cis- and trans-permethrin isomers and their major urinary metabolites in rats. Toxicol Appl Pharmacol. 2016;294:65–77.

    Article  CAS  PubMed  Google Scholar 

  17. Côté J, Bonvalot Y, Carrier G, Lapointe C, Fuhr U, Tomalik-Scharte D, et al. A novel toxicokinetic modeling of cypermethrin and permethrin and their metabolites in humans for dose reconstruction from biomarker data. PLoS One. 2014;9:e88517.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Tornero-Velez R, Davis J, Scollon EJ, Starr JM, Setzer RW, Goldsmith M-R, et al. A pharmacokinetic model of cis- and trans-permethrin disposition in rats and humans with aggregate exposure application. Toxicol Sci. 2012;130:33–47.

    Article  CAS  PubMed  Google Scholar 

  19. Leng G, Kühn K-H, Idel H. Biological monitoring of pyrethroids in blood and pyrethroid metabolites in urine: applications and limitations. Sci Total Environ. 1997;199:173–81.

    Article  CAS  Google Scholar 

  20. Toledo Netto P, Teixeira Júnior OJ, de Camargo JLV, Lúcia Ribeiro M, de Marchi MRR. A rapid, environmentally friendly, and reliable method for pesticide analysis in high-fat samples. Talanta. 2012;101:322–9.

    Article  CAS  PubMed  Google Scholar 

  21. Du J, Yan H, She D, Liu B, Yang G. Simultaneous determination of cypermethrin and permethrin in pear juice by ultrasound-assisted dispersive liquid-liquid microextraction combined with gas chromatography. Talanta. 2010;82:698–703.

    Article  CAS  PubMed  Google Scholar 

  22. Lestremau F, Willemin M-E, Chatellier C, Desmots S, Brochot C. Determination of cis-permethrin, trans-permethrin and associated metabolites in rat blood and organs by gas chromatography–ion trap mass spectrometry. Anal Bioanal Chem. 2014;406:3477–87.

    Article  CAS  PubMed  Google Scholar 

  23. Hooshfar S, Gullick DR, Linzey MR, Mortuza T, Abdel Rahman MH, Rogers CA, et al. Simultaneous determination of cis-permethrin and trans-permethrin in rat plasma and brain tissue using gas chromatography–negative chemical ionization mass spectrometry. J Chromatogr B. 2017;1060:291–9.

    Article  CAS  Google Scholar 

  24. Bielawski D, Ostrea E, Posecion N, Corrion M, Seagraves J. Detection of several classes of pesticides and metabolites in meconium by gas chromatography-mass spectrometry. Chromatographia. 2005;62:623–9.

    Article  CAS  Google Scholar 

  25. Berkowitz GS, Obel J, Deych E, Lapinski R, Godbold J, Liu Z, et al. Exposure to indoor pesticides during pregnancy in a multiethnic, urban cohort. Environ Health Perspect. 2002;111:79–84.

    Article  Google Scholar 

  26. Starr JM, Graham SE, Ross DG, Tornero-Velez R, Scollon EJ, DeVito MJ, et al. Environmentally relevant mixing ratios in cumulative assessments: a study of the kinetics of pyrethroids and their ester cleavage metabolites in blood and brain; and the effect of a pyrethroid mixture on the motor activity of rats. Toxicology. 2014;320:15–24.

    Article  CAS  PubMed  Google Scholar 

  27. Official Journal of the European Union. Directive 2010/63/EU of the European Parliament and of the Council of the 22 September 2010 on the protection of animals used for scientific purposes. 2010.

  28. The European Agency for the Evaluation of Medical Products. Guideline on bioanalytical method validation. EMEA/CHMP/EWP/192217/2009 Rev1. Corr.2. 2011.

  29. Commission E. Guidance document on analytical quality control and method validation procedures for pesticides residues analysis in food and feed. SANTE/ 11945/2015. Brussels. 2015.

  30. Abu-Qare AW, Abou-Donia MB. Simultaneous determination of chlorpyrifos, permethrin, and their metabolites in rat plasma and urine by high-performance liquid chromatography. J Anal Toxicol. 2001;25:275–9.

    Article  CAS  Google Scholar 

  31. Anadon A, Martinez-Larranaga MR, Diaz MJ, Bringas P. Toxicokinetics of permethrin in the rat. Toxicol Appl Pharmacol. 1991;110:1–8.

    Article  CAS  Google Scholar 

  32. New L-S, Chan ECY. Evaluation of BEH C18, BEH HILIC, and HSS T3 (C18) column chemistries for the UPLC-MS-MS analysis of glutathione, glutathione disulfide, and ophthalmic acid in mouse liver and human plasma. J Chromatogr Sci. 2008;46:209–14.

    Article  CAS  PubMed  Google Scholar 

  33. Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF. In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome P450 isoforms. Drug Metab Dispos. 2009;37:221–8.

    Article  CAS  PubMed  Google Scholar 

Download references


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.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Florence Zeman.

Ethics declarations

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).

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: