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GC-MS analysis of ethanol and other volatile compounds in micro-volume blood samples—quantifying neonatal exposure

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Abstract

A static headspace gas chromatography coupled mass spectrometry (GC-MS) method was developed and fully validated for the quantitative measurement of acetaldehyde, acetone, methanol, ethanol and acetic acid in the headspace of micro-volumes of blood using n-propanol as an internal standard. The linearity of the method was established over the range 0.2–100 mg/L (R 2 > 0.99) and the limits of detection were 0.1–0.2 mg/L and lower limits quantification 0.5–1 mg/L. Precision and accuracies fell within acceptable limits (20 % for LLOQ and 15 %) for both intra- and inter-day analyses for all compounds except acetaldehyde which had inter-day variability of ≤25 %. The method was applied to analyse blood samples from neonatal patients receiving courses of ethanol excipient containing medications. Baseline levels of acetaldehyde, acetone, methanol and ethanol could be measured in patients before dosing commenced and an increase in levels of some volatiles were observed in several neonates after receiving ethanol-containing medications.

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References

  1. Ziavrou K, Boumba VA, Vougiouklakis TG (2005) Insights into the origin of postmortem ethanol. Int J Toxicol 24:69–77

    Article  CAS  Google Scholar 

  2. Kugelberg FC, Jones AW (2007) Interpreting results of ethanol analysis in postmortem specimens: a review of the literature. Forensic Sci Int 165:10–29

    Article  CAS  Google Scholar 

  3. De Martinis BS, Martin CC (2002) Automated headspace solid-phase microextraction and capillary gas chromatography analysis of ethanol in postmortem specimens. Forensic Sci Int 128:115–119

    Article  Google Scholar 

  4. Zuba D, Piekoszewski W, Pach J, Winnik L, Parczewski A (2002) Concentration of ethanol and other volatile compounds in the blood of acutely poisoned alcoholics. Alcohol 26:17–22

    Article  CAS  Google Scholar 

  5. Dubowski KM (1980) Alcohol determination in the clinical laboratory. Am J Clin Pathol 74:747–750

    CAS  Google Scholar 

  6. Christophersen AS, Gjerde H, Bjorneboe A, Sakshaug J, Morland J (1990) Screening for drug use among Norwegian drivers suspected of driving under influence of alcohol or drugs. Forensic Sci Int 45:5–14

    Article  CAS  Google Scholar 

  7. Jones AW, Beylich KM, Bjorneboe A, Ingum J, Morland J (1992) Measuring ethanol in blood and breath for legal purposes: variability between laboratories and between breath-test instruments. Clin Chem 38:743–747

    CAS  Google Scholar 

  8. Keim ME, Bartfield JM, Raccio-Robak N, Abhyankar VV, Salluzzo RF (1999) Accuracy of an enzymatic assay device for serum ethanol measurement. J Toxicol Clin Toxicol 37:75–81

    Article  CAS  Google Scholar 

  9. Hadjiioannou TP, Hadjiioannou SI, Avery J, Malmstadt HV (1976) Automated enzymic determination of ethanol in blood, serum, and urine with a miniature centrifugal analyzer. Clin Chem 22:802–805

    CAS  Google Scholar 

  10. Pontes H, de Pinho PG, Casal S, Carmo H, Santos A, Magalhaes T, Remiao F, Carvalho F, Bastos ML (2009) GC determination of acetone, acetaldehyde, ethanol, and methanol in biological matrices and cell culture. J Chromatogr Sci 47:272–278

    CAS  Google Scholar 

  11. Tangerman A (1997) Highly sensitive gas chromatographic analysis of ethanol in whole blood, serum, urine, and fecal supernatants by the direct injection method. Clin Chem 43:1003–1009

    CAS  Google Scholar 

  12. Seto Y (1994) Determination of voaltile substances in biological samples by headspace gas-chromatography. J Chromatogr A 674:25–62

    Article  CAS  Google Scholar 

  13. Jones AW, Fransson M (2003) Blood analysis by headspace gas chromatography: does a deficient sample volume distort ethanol concentration? Med Sci Law 43:241–247

    Article  CAS  Google Scholar 

  14. Kristoffersen L, Stormyhr L-E, Smith-Kielland A (2006) Headspace gas chromatographic determination of ethanol: the use of factorial design to study effects of blood storage and headspace conditions on ethanol stability and acetaldehyde formation in whole blood and plasma. Forensic Sci Int 161:151–157

    Article  CAS  Google Scholar 

  15. Macchia T, Mancinelli R, Gentili S, Lugaresi EC, Raponi A, Taggi F (1995) Ethanol in biological fluids—headspace GC measurement. J Anal Toxicol 19:241–246

    CAS  Google Scholar 

  16. Portari GV, Marchini JS, Jordao AA (2008) Validation of a manual headspace gas chromatography method for determining volatile compounds in biological fluids. Labmedicine 39:42–45

    Google Scholar 

  17. De Martinis BS, Ruzzene MAM, Martin CCS (2004) Determination of ethanol in human blood and urine by automated headspace solid-phase microextraction and capillary gas chromatography. Anal Chim Acta 522:163–168

    Article  Google Scholar 

  18. Zuba D, Parczewski A, Reichenbacher M (2002) Optimization of solid-phase microextraction conditions for gas chromatographic determination of ethanol and other volatile compounds in blood. J Chromatogr B Anal Technol Biomed Life Sci 773:75–82

    Article  CAS  Google Scholar 

  19. Wasfi IA, Al-Awadhi AH, Al-Hatali ZN, Al-Rayami FJ, Al Katheeri NA (2004) Rapid and sensitive static headspace gas chromatography–mass spectrometry method for the analysis of ethanol and abused inhalants in blood. J Chromatogr B 799:331–336

    Article  CAS  Google Scholar 

  20. Watanabe-Suzuki K, Seno H, Ishii A, Kumazawa T, Suzuki O (1999) Ultra-sensitive method for determination of ethanol in whole blood by headspace capillary gas chromatography with cryogenic oven trapping. J Chromatogr B Anal Technol Biomed Life Sci 727:89–94

    Article  CAS  Google Scholar 

  21. Armstrong NA (1997) Functionality related tests for excipients. Int J Pharm 155:1–5

    Article  CAS  Google Scholar 

  22. Pifferi G, Restani P (2003) The safety of pharmaceutical excipients. Il Farmaco 58:541–550

    Article  CAS  Google Scholar 

  23. Osterberg RE, See NA (2003) Toxicity of excipients—a food and drug administration perspective. Int J Toxicol 22:377–380

    CAS  Google Scholar 

  24. Whittaker A, Currie AE, Turner MA, Field DJ, Mulla H, Pandya HC (2009) Toxic additives in medication for preterm infants. Arch Dis Child Fetal Neonatal Ed 94:F236–F240

    Article  CAS  Google Scholar 

  25. Shehab N, Lewis CL, Streetman DD, Donn SM (2009) Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med 10:256–259

    Article  Google Scholar 

  26. Crato H, Walther G, Herrmann A (1978) The occurrence of acetone in blood samples forwarded for alcohol content analysis. Beitr Gerichtl Med 36:275–279

    CAS  Google Scholar 

  27. Iffland R, Grassnack F (1995) Epidemiologic study of CDT (carbohydrate-deficient transferrin) and other indicators of alcohol problems in high blood alcohol German automobile drivers. Blutalkohol 32:26–41

    CAS  Google Scholar 

  28. Food and Drug Administration, Guidance for Industry Process Validation: General Principles and Practices, 2011

  29. Graham S, Turner M (2011) European Study of Neonatal Exposure to Excipients (ESNEE). Infant 7:196–199

    Google Scholar 

  30. Alonso M, Castellanos M, Besalu E, Sanchez JM (2012) A headspace needle-trap method for the analysis of volatile organic compounds in whole blood. J Chromatogr A 1252:23–30

    Article  CAS  Google Scholar 

  31. Ashley DL, Bonin MA, Cardinali FL, McCraw JM, Holler JS, Needham LL, Patterson DG Jr (1992) Determining volatile organic compounds in human blood from a large sample population by using purge and trap gas chromatography/mass spectrometry. Anal Chem 64:1021–1029

    Article  CAS  Google Scholar 

  32. Lewis SJ, Zuccolo L, Davey Smith G, Macleod J, Rodriguez S, Draper ES, Barrow M, Alati R, Sayal K, Ring S, Golding J, Gray R (2012) Fetal alcohol exposure and IQ at age 8: evidence from a population-based birth-cohort study. PLoS One 7:e49407

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The work described here was funded by the ESNEE project which is conducted under ERA-NET PRIOMEDCHILD. In the UK, this is funded by MRC Grant G1100158 to Dr. Mark A. Turner. The authors acknowledge the contribution of Rosalind Astles with sampling and consent.

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Correspondence to Paul S. Monks.

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Cordell, R.L., Pandya, H., Hubbard, M. et al. GC-MS analysis of ethanol and other volatile compounds in micro-volume blood samples—quantifying neonatal exposure. Anal Bioanal Chem 405, 4139–4147 (2013). https://doi.org/10.1007/s00216-013-6809-1

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  • DOI: https://doi.org/10.1007/s00216-013-6809-1

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