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.
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REFERENCES
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).
J. Holmstrand, E. Änggard, and L. Gunne. Methadone maintenance plasma levels and therapeutic outcome. Clin. Pharmacol. Ther. 23(2):175–180 (1978).
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.
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.
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).
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).
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).
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).
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.
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).
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).
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).
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).
H. E. Hamilton, J. E. Wallace, and K. Blum. Improved methods for quantitative determination of methadone. J. Pharm. Sci. 63:741–745 (1974).
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).
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).
P. Hartwig and B. Näslund. Electron-capture gas chromatography of methadone after oxidation to benzophenone. J. Chromatogr. 111:347–354 (1975).
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).
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).
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).
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).
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).
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).
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).
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).
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).
M. Rowland and T. N. Tozer. Clinical Pharmacokinetics: Concepts and Applications, Lea & Febiger, Philadelphia, London, 1989.
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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
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DOI: https://doi.org/10.1023/A:1018904825958