Skip to main content
Log in

Rapid Determination of Methadone in Plasma, Cerebrospinal Fluid, and Urine by Gas Chromatography and Its Application to Routine Drug Monitoring

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Determination of methadone (MET) in biological fluids can serve to adjust dosages in patients suffering from cancer pain or participating in methadone maintenance programs. We developed a gas chromatographic assay using nitrogen-phosphorus detection. The method involves a single-step extraction from alkalized plasma, cerebrospinal fluid, or urine into n-hexane/isoamylalcohol (99/1, v/v). Dextropropoxyphene was used as internal standard. Separation was achieved with a silica SE-52-CB column (13 m × 0.25-mm I.D.). The method was validated for the determination of MET in plasma, urine, and cerebrospinal fluid with a quantification limit of 0.5 ng/ mL. The coefficients of variation for within-day and between-day precision were within 10.2 and 14.1%, respectively. Approximately 100 samples can be analyzed by one person in the course of a working day, making the method applicable to routine drug monitoring. The method was demonstrated to be sensitive and accurate for pharmacokinetic studies in plasma, urine, or cerebrospinal fluid.

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. C. E. Inturrisi, W. A. Colburn, R. F. Kaiko, R. W. Houde, and K. M. Foley. Pharmacokinetics and pharmacodynamics of methadone in patients with chronic pain. Clin Pharmacol. Ther. 41:392 (1987).

    Google Scholar 

  2. J. Holmstrand, E. Änggard, and L. Gunne. Methadone maintenance plasma levels and therapeutic outcome. Clin. Pharmacol. Ther. 23(2):175–180 (1978).

    Google Scholar 

  3. L. E. Mather and D. D. Denson. Pharmacokinetic considerations for drug dosing. In P. P. Raj (ed.), Practical Management of Pain, Year Book, Chicago, London, 1986, p. 489.

    Google Scholar 

  4. G. K. Gourlay, M. J. Cousins, and D. A. Cherry. Drug therapy. In G. D. Burrows, D. Elton, and G. V. Stanley (eds.), Handbook of Chronic Pain Management, Elsevier, Amsterdam, New York, Oxford, 1987, p. 163.

    Google Scholar 

  5. U. Meresaar, M. I. Nilsson, J. Holmstrand, and E. Änggard. Single dose pharmacokinetics and bioavailability of methadone in man studied with a stable isotope method. Eur. J. Clin. Pharmacol. 20:473–478 (1981).

    Google Scholar 

  6. R. K. Lynn, R. M. Leger, W. P. Gordon, G. D. Olsen, and N. Gerber. New gas chromatographic assay for the quantification of methadone. J. Chromatogr. 131:329–340 (1977).

    Google Scholar 

  7. G. K. Gourlay, R. J. Willis, and P. R. Wilson. Postoperative pain control with methadone: Influence of supplementary methadone doses and blood concentration-response relationships. Anesthesiology 61:19–26 (1984).

    Google Scholar 

  8. J. Säwe, J. Hansen, C. Ginman, P. Hartvig, P. A. Jakobsson, M. I. Nilsson, A. Rasse, and E. Änggard. Patient-controlled dose regimen of methadone for chronic cancer pain. Br. Med. J. 7:771–773 (1981).

    Google Scholar 

  9. R. L. Foltz, A. F. Fentiman, and R. B. Foltz. GC/MS assays for abused drugs in body fluids. NIDA Research Monograph No. 32, U.S. Government Printing Office. Washington, D.C., Aug. 1980, pp. 51–61.

    Google Scholar 

  10. I. K. Ho, H. H. Loh, and E. L. Way. Mini thin-layer chromatography in the detection of narcotics in urine from subjects on a methadone maintenance program. J. Chromatogr. 65:577–579 (1972).

    Google Scholar 

  11. J. Montalvo, E. Klein, D. Eger, and B. Herper. Identification of drugs of abuse in urine. A study of the Dole technique. J. Chromatogr. 47:542–545 (1970).

    Google Scholar 

  12. J. S. F. Ling, J. G. Umans, and C. E. Inturrisi. Methadone: Radioimmunoassay and pharmacokinetics in the rat. J. Pharmacol. Exp. Ther. 217:147–151 (1981).

    Google Scholar 

  13. F. Bartos, G. D. Olsen, R. N. Leger, and D. Bartos. Stereospecific antibodies to methadone I. Radioimmunoassay of d,I-methadone in human serum. Chem. Pathol. Pharmacol. 16:131–143 (1977).

    Google Scholar 

  14. H. E. Hamilton, J. E. Wallace, and K. Blum. Improved methods for quantitative determination of methadone. J. Pharm. Sci. 63:741–745 (1974).

    Google Scholar 

  15. J. E. Wallace, H. E. Hamilton, J. T. Payte, and K. Blum. Sensitive spectrophotometric method for determining methadone in biological specimens. J. Pharm. Sci. 61:1397–1400 (1972).

    Google Scholar 

  16. C. E. Inturrisi and K. Verebely. A gas-liquid chromatographic method for quantitative determination of methadone in human plasma and urine. J. Chromatogr. 65:361–369 (1972).

    Google Scholar 

  17. P. Hartwig and B. Näslund. Electron-capture gas chromatography of methadone after oxidation to benzophenone. J. Chromatogr. 111:347–354 (1975).

    Google Scholar 

  18. P. Jacob, J. F. Rigod, S. M. Poud, and N. L. Benowitz. Determination of methadone and its primary metabolite in biologic fluids using gas chromatography with nitrogen-phosphorus detection. J. Anal. Toxicol. 5:292–295 (1981).

    Google Scholar 

  19. F. Magora, J. Chrubasik, D. Damm, J. Schulte-Mönting, and Y. Shir. Application of a new method for measurement of plasma methadone levels to the use of epidural methadone for relief of postoperative pain. Anesth. Analg. 66:1308–1311 (1987).

    Google Scholar 

  20. K. Wolff, M. Sanderson, A. W. M. Hay, and D. Raistrick. Methadone concentrations in plasma and their relationship to drug dosage. Clin. Chem. 37/2:205–209 (1991).

    Google Scholar 

  21. H. Derendorf and E. R. Garret, High-performance liquid chromatographic assay of methadone, phencyclidine, and metabolites by postcolumn ion-pair extraction and on-line fluorescent detection of the counterion with applications. J. Pharm. Sci. 72:630–635 (1983).

    Google Scholar 

  22. E. R. Garret, H. Derendorf, and A. G. Mattha. Pharmacokinetics of Morphine and its surrogates VII: High-performance liquid chromatographic analyses and pharmacokinetics of methadone and its derived metabolites in dogs. J. Pharm. Sci. 74:1203–1214 (1985).

    Google Scholar 

  23. L. D. Baugh, R. H. Lin, and A. S. Walia. Simultaneous gas chromatography/mass spectrometry assay of methadone and 2-ethyl-1,5-diphenylpyrrolidine (EDDP) in urine. J. Forens. Sci. 36(2):548–555 (1991).

    Google Scholar 

  24. H. R. Sullivan, F. J. Marshall, R. E. McMahon, E. Änggard, L.-M. Gunne, and J. H. Holmstrand. Mass fragmentographic determination of unlabeled and deuterium labeled methadone in human plasma. Possibilities for measurement of steady state pharmacokinetics. Biomed. Mass. Spectrom. 2:197–200 (1975).

    Google Scholar 

  25. D. L. Hachey, M. J. Kreek, and D. H. Mattson. Quantitative analysis of methadone in biological fluids using deuterium-labeled methadone and GLC-Chemical-Ionization mass spectrometry. J. Pharm. Sci. 66:1579–1582 (1977).

    Google Scholar 

  26. K. Nakamura, D. L. Hachey, M. J. Kreek, C. S. Iriving, and P. D. Klein. Quantitation of methadone enantiomers in humans using stable isotope-labeled [2H3], [2H5]-, and [2H8]-methadone. J. Pharm. Sci. 71:40–43 (1982).

    Google Scholar 

  27. M. Rowland and T. N. Tozer. Clinical Pharmacokinetics: Concepts and Applications, Lea & Febiger, Philadelphia, London, 1989.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schmidt, N., Sittl, R., Brune, K. et al. Rapid Determination of Methadone in Plasma, Cerebrospinal Fluid, and Urine by Gas Chromatography and Its Application to Routine Drug Monitoring. Pharm Res 10, 441–444 (1993). https://doi.org/10.1023/A:1018904825958

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018904825958

Navigation