Skip to main content
Log in

Simultaneous determination of therapeutic plasma concentrations of pethidine and norpethidine in man by electron capture gas chromatography

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

An analytical procedure for the simultaneous determination of pethidine and its N-Demethylated metabolite, norpethidine, in plasma is described. Pethidine and norpethidine are separated by partition chromatography, converted to the trichloroethyl carbamate with trichloroethyl chloroformate and determined by electron capture gas chromatography. The smallest amounts of pethidine and norpethidine determined by the method were 10 and 2 ng, respectively, in 0.1 ml plasma. The relative standard deviation in the determination of 50 ng of pethidine and 40 ng of norpethidine in 0.1 ml plasma were 5.8% (n=8) and 6.3% (n=10), respectively. The method was used to determine plasma levels of pethidine and norpethidine in three patients who received subcutaneous doses of pethidine 50–75 mg for postoperative pain. The peak levels of pethidine were found to be in the range 200–400 ng/ml, with a plasma half-life of the order of 4 hours. The levels of norpethidine were low.

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.

Similar content being viewed by others

References

  1. Plotnikoff, N. P., Elliott, H. W., Way, E. L.: The metabolism of N-14CH3 labeled meperidine. J. Pharmacol. exp. Ther.104, 377–386 (1952)

    Google Scholar 

  2. Plotnikoff, N. P., Way, E. L., Elliott, H. W.: Biotransformation products of meperidine excreted in the urine of man. J. Pharmacol. exp. Ther.117, 414–419 (1956)

    Google Scholar 

  3. Burns, J. J., Berger, B. L., Lief, P. A., Wollack, A., Papper, E. M., Brodie, B. B.: The physiological disposition and fate of meperidine (Demerol) in man and a method for its estimation in plasma. J. Pharmacol. exp. Ther.114, 289–298 (1955)

    Google Scholar 

  4. Asatoor, A. M., London, D. R., Milne, M. D., Simenhoff, M. L.: The excretion of pethidine and its derivatives. Brit. J. Pharmacol.20, 285–298 (1963)

    Google Scholar 

  5. Miller, J. W., Anderson, H. H.: The effect of N-demethylation on certain pharmacologic actions of morphine, codeine, and meperidine in the mouse. J. Pharmacol. exp. Ther.112, 191–196 (1954)

    Google Scholar 

  6. Deneau, G. A., Nakai, K.: Type of toxicity in the monkey as influenced by the rate of metabolic conversion of meperidine to normeperidine. Pharmacologist2, 98 (1960)

    Google Scholar 

  7. Knowles, J. A., White, G. R., Ruelius, H. W.: Determination of meperidine in human plasma and urine by gas-liquid chromatography. Anal. Letters6, 281–290 (1973)

    Google Scholar 

  8. Klotz, U., McHorse, T. S., Wilkinson, G. R., Schenker, S.: The effect of cirrhosis on the disposition and elimination of meperidine in man. Clin. Pharmacol. Ther.16, 667–675 (1974)

    Google Scholar 

  9. Chan, K., Kendall, M. J., Mitchard, M.: A quantitative gasliquid chromatographic method for the determination of pethidine and its metabolites, norpethidine and pethidine N-oxide, in human biological fluids. J. Chromatogr.89, 169–176 (1974)

    Google Scholar 

  10. Hartvig, P., Karlsson, K.-E., Johansson, L., Lindberg, C.: Determination of pethidine in plasma by electron capture gas chromatography after reaction with trichloroethyl chloroformate. J. Chromatogr.121, 235–242 (1976)

    Google Scholar 

  11. Lindberg, C., Bogentoft, C., Danielsson, B.: Mass spectrometry of pethidine and pethidine metabolites. A study utilizing specifically deuterated pethidine. Acta pharm. suec.11, 201–210 (1974)

    Google Scholar 

  12. Merck & Co., Inc.: Substituted piperidines. Brit. Pat. 840,006 (1960); Chem. Abstr.55, 6502g (1961)

  13. Westerlund, D., Borg, K. O.: Fluorimetric determinations by ion pair extraction. Acta pharm. suec.7, 267–278 (1970)

    Google Scholar 

  14. Borg, K. O., Mikaelsson, A.: Fluorimetric determination of pentazocine in biological samples by partition chromatography as ion pair in micro-columns. Acta pharm. suec.7, 673–680 (1970)

    Google Scholar 

  15. Matzner, M., Kurkjy, R. P., Cotter, R. J.: The chemistry of chloroformates. Chem. Rev.64, 645–687 (1964)

    Google Scholar 

  16. Gejvall, T.: Gas chromatographic analysis of amines separated as urethane derivatives. J. Chromatogr.90, 157–161 (1974)

    Google Scholar 

  17. Stambaugh, J. E., Wainer, I. W.: The bioavailability of meperidine. J. clin. Pharmacol.14, 552–559 (1974)

    Google Scholar 

  18. Mather, L. E., Tucker, G. T., Pflug, A. E., Lindop, M. J., Wilkerson, C.: Meperidine kinetics in man. Intravenous injection in surgical patients and volunteers. Clin. Pharmacol. Ther.17, 21–30 (1975)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hartvig, P., Karlsson, K.E., Lindberg, C. et al. Simultaneous determination of therapeutic plasma concentrations of pethidine and norpethidine in man by electron capture gas chromatography. Eur J Clin Pharmacol 11, 65–69 (1977). https://doi.org/10.1007/BF00561790

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00561790

Key words

Navigation