Analytical and Bioanalytical Chemistry

, Volume 409, Issue 26, pp 6123–6131 | Cite as

Towards quantification of toxicity of lithium ion battery electrolytes - development and validation of a liquid-liquid extraction GC-MS method for the determination of organic carbonates in cell culture materials

  • Jenny Strehlau
  • Till Weber
  • Constantin Lürenbaum
  • Julia Bornhorst
  • Hans-Joachim Galla
  • Tanja Schwerdtle
  • Martin Winter
  • Sascha NowakEmail author
Research Paper


A novel method based on liquid-liquid extraction with subsequent gas chromatography separation and mass spectrometric detection (GC-MS) for the quantification of organic carbonates in cell culture materials is presented. Method parameters including the choice of extraction solvent, of extraction method and of extraction time were optimised and the method was validated. The setup allowed for determination within a linear range of more than two orders of magnitude. The limits of detection (LODs) were between 0.0002 and 0.002 mmol/L and the repeatability precisions were in the range of 1.5–12.9%. It could be shown that no matrix effects were present and recovery rates between 98 and 104% were achieved. The methodology was applied to cell culture models incubated with commercial lithium ion battery (LIB) electrolytes to gain more insight into the potential toxic effects of these compounds. The stability of the organic carbonates in cell culture medium after incubation was studied. In a porcine model of the blood-cerebrospinal fluid (CSF) barrier, it could be shown that a transfer of organic carbonates into the brain facing compartment took place.

Graphical abstract

Schematic setup for the investigation of toxicity of lithium ion battery electrolytes


Liquid-liquid extraction GC-MS Lithium ion battery (LIB) Organic carbonates Cell culture materials 



This work was supported by the German Federal Ministry of Education and Research (BMBF) within the project “SafeBatt” (project grant numbers 03X4631N and 03X4631Q).

Compliance with ethical standards

The primary cultures were obtained from the brains of freshly slaughtered pigs. The brains were collected from a slaughterhouse. The clear advantage is the alternative to the costly, time-consuming and ethically questionable systems derived from experimental animals.

Conflict of interest

The authors have no potential conflict of interest.

Supplementary material

216_2017_549_MOESM1_ESM.pdf (252 kb)
ESM 1 (PDF 251 kb)


  1. 1.
    Kalhoff J, Eshetu GG, Bresser D, Passerini S. Safer electrolytes for lithium-ion batteries: state of the art and perspectives. ChemSusChem. 2015;8:2154–75.CrossRefGoogle Scholar
  2. 2.
    Besenhard JO, Werner K, Winter M. Fluorhaltige Lösungsmittel für Lithiumbatterien mit erhöhter Sicherheit. German Patent DE196191233A1; 1996.Google Scholar
  3. 3.
    Schmitz RW, Murmann P, Schmitz R, Müller R, Krämer L, Kasnatscheew J, et al. Investigations on novel electrolytes, solvents and SEI additives for use in lithium-ion batteries: systematic electrochemical characterization and detailed analysis by spectroscopic methods. Prog Solid State Chem. 2014;42:65–84.Google Scholar
  4. 4.
    Brox S, Roeser S, Husch T, Hildebrand S, Fromm O, Korth M, et al. Alternative single-solvent electrolytes based on cyanoesters for safer lithium-ion batteries. ChemSusChem. 2016;13:1704–11.Google Scholar
  5. 5.
    Möller KC, Hodal T, Appel WK, Winter M, Besenhard JO. Fluorinated organic solvents in electrolytes for lithium ion cells. J Power Sources. 2001;97-98:595–7.CrossRefGoogle Scholar
  6. 6.
    Ribière P, Grugeon S, Morcrette M, Boyanov S, Laruelle S, Marlair G. Investigation on the fire-induced hazards of lithium-ion battery cells by fire calorimetry. Energy Environ Sci. 2012;22:5271–80.CrossRefGoogle Scholar
  7. 7.
    Gachot G, Grugeon S, Eshetu GG, Mathiron D, Ribière P, Armand M, et al. Thermal behaviour of the lithiated-graphite/electrolyte interface through GC/MS analysis. Electrochim Acta. 2012;83:402–9.Google Scholar
  8. 8.
    Terborg L, Weber S, Passerini S, Winter M, Karst U, Nowak S. Development of gas chromatographic methods for the analyses of organic carbonate-based electrolytes. J Power Sources. 2014;245:836–40.CrossRefGoogle Scholar
  9. 9.
    Grützke M, Kraft V, Hofmann B, Klamor S, Diekmann J, Kwade A, et al. Aging investigations of a lithium-ion battery electrolyte from a field-tested hybrid electric vehicle. J Power Sources. 2015;273:83–8.Google Scholar
  10. 10.
    Grützke M, Kraft V, Weber W, Wendt C, Friesen A, Klamor S, et al. Supercritical carbon dioxide extraction of lithium-ion battery electrolytes. J Supercrit Fluids. 2014;94:216–22.Google Scholar
  11. 11.
    Grützke M, Mönninghoff X, Horsthemke F, Kraft V, Winter M, Nowak S. Extraction of lithium-ion battery electrolytes with liquid and supercritical carbon dioxide and additional solvents. RSC Adv. 2015;5:43209–17.CrossRefGoogle Scholar
  12. 12.
    Sloop SE, Pugh JK, Wang S, Kerr JB, Kinoshita K. Chemical reactivity of PF5 and LiPF6 in ethylene carbonate dimethyl carbonate solutions. Electrochem Solid-State Lett. 2001;4:A42–4.CrossRefGoogle Scholar
  13. 13.
    Sloop SE, Kerr JB, Kinoshita K. The role of Li-ion battery electrolyte reactivity in performance decline and self-discharge. J Power Sources. 2003;119-121:330–7.CrossRefGoogle Scholar
  14. 14.
    Petibon R, Rotermund L, Nelson KJ, Gozdz AS, Xia J, Dahn JR. Study of electrolyte components in Li ion cells using liquid-liquid extraction and gas chromatography coupled with mass spectrometry. J Electrochem Soc. 2014;161:A1167–72.CrossRefGoogle Scholar
  15. 15.
    Bornhorst J, Wehe CA, Hüwel S, Karst U, Galla HJ, Schwerdtle T, Impact of manganese on and transfer across blood-brain and blood-cerebrospinal fluid barrier in vitro. jbc. 2012;287:17140–51.Google Scholar
  16. 16.
    Angelow S, Zeni P, Galla HJ. Usefulness and limitation of primary cultured porcine choroid plexus epithelial cells as an in vitro model to study drug transport at the blood–CSF barrier. Adv Drug Deliv Rev. 2004;56:1859–73.CrossRefGoogle Scholar
  17. 17.
    Cammann K. Instrumentelle Analytische Chemie, Heidelberg:Spektrum Akademischer Verlag; 2001.Google Scholar
  18. 18.
    Kromidas S. Handbuch Validierung in der Analytik, Weinheim:WILEY-VCH; 2011.Google Scholar
  19. 19.
    Küster FW, Thiel A. Rechentafeln für die chemische Analytik, Berlin:Walter de Gruyter; 2003.Google Scholar
  20. 20.
    Currie LA, Svehla G. Nomenclature for the presentation of results of chemical analysis. Pure Appl Chem. 1994;66:595–608.CrossRefGoogle Scholar
  21. 21.
    Shah VP, Midha KK, Dighe D, McGilveray IJ, Skelly JP, Yacobi A, et al. Analytical methods validation: bioavailability. Bioequivalence Pharmacokinet Stud Pharm Res. 1992;9:588–92.Google Scholar
  22. 22.
    Shah VP, Midha KK, Findlay JWA, Hill HM, Hulse JD, McGilveray IJ, et al. Bioanalytical method validation—a revisit with a decade of progress. Pharm Res. 2000;17:1551–6.Google Scholar
  23. 23.
    Brüggemann L, Quapp W, Wennrich R. Test for non-linearity concerning linear calibrated chemical measurements. Accred Qual Assur. 2006;11:625–31.CrossRefGoogle Scholar
  24. 24.
    Funk W, Dammann V, Couturier T, Schiller J, Völker L. Quantitative HPTLC determination of selenium. J High Resolut Chromatogr Chromatogr Commun. 1986;9:224–35.CrossRefGoogle Scholar
  25. 25.
    Hartmann C, Smeyers-Verbeke J, Massart DL, McDowall RD. Validation of bioanalytical chromatographic methods. J Pharm Biomed Anal. 1998;17:193–218.CrossRefGoogle Scholar
  26. 26.
    Westgard JO. Hunt MR use and interpretation of common statistical tests in method-comparison studies. Clin Chem. 1973;19:49–57.Google Scholar
  27. 27.
    Funk W, Dammann V, Vonderheid C, Oelmann G. Statistische Methoden in der Wasseranalytik. Weinheim:VCH; 1985.Google Scholar
  28. 28.
    AOAC International , Official methods of analysis, appendix f: guidelines for standard method performance requirements; 2012.Google Scholar
  29. 29.
    Xu K. Nonaqueous liquid electrolytes for lithium-based rechargeable batteries. Chem Rev. 2004;104:4303–417.CrossRefGoogle Scholar
  30. 30.
    Lohren H, Bornhorst J, Galla HJ, Schwerdtle T. The blood-cerebrospinal fluid barrier-first evidence for an active transport of organic mercury compounds out of the brain. Metallomics. 2015;7:1420–30.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Jenny Strehlau
    • 1
  • Till Weber
    • 2
  • Constantin Lürenbaum
    • 1
  • Julia Bornhorst
    • 2
  • Hans-Joachim Galla
    • 3
  • Tanja Schwerdtle
    • 2
  • Martin Winter
    • 1
    • 4
  • Sascha Nowak
    • 1
    Email author
  1. 1.MEET Battery Research Center, Institute of Physical ChemistryUniversity of MünsterMünsterGermany
  2. 2.Department of Food Chemistry, Institute of Nutritional ScienceUniversity of PotsdamNuthetalGermany
  3. 3.Institute of BiochemistryUniversity of MünsterMünsterGermany
  4. 4.Helmholtz-Institute Münster (HI MS)MünsterGermany

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