Quantitation of methadone enantiomers in humans using stable isotope-labeled (2H3)-, (2H5)-, and (2H8)Methadone
A new technique for simultaneous stereoselective kinetic studies of methadone enantiomers was developed using three deuterium-labeled forms of methadone and GLC-chemical-ionization mass spectrometry. A racemic mixture (1:1) of (R)-(-)-(2H5)methadone (l-form) and (S)-(R)-(2H3)methadone (d-form) was administered orally in place of a single daily dose of unlabeled (+/-)-(2H0)methadone in long-term maintenance patients. Racemic (+/-)-(2H8)methadone was used as an internal standard for the simultaneous quantitation of (2H0)-, (2H3)-, and (2H5)methadone in plasma and urine. A newly developed extraction procedure, using a short, disposable C18 reversed-phase cartridge and improved chemical-ionization procedures employing ammonia gas, resulted in significant reduction of the background impurities contributing to the ions used for isotopic abundance measurements. These improvements enabled the measurement of labeled plasma methadone levels for 120 hr following a single dose. This methodology was applied to the study of methadone kinetics in two patients; in both patients, the analgesically active l-enantiomer of the drug had a longer plasma elimination half-life and a smaller area under the plasma disappearance curve than did the inactive d-form.
- Research Organization:
- Division of Biological and Medical Research, Argonne National Laboratory, IL
- OSTI ID:
- 5555613
- Journal Information:
- J. Pharm. Sci.; (United States), Vol. 71:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ORGANIC
PHYSICAL AND ANALYTICAL CHEMISTRY
DEUTERIUM COMPOUNDS
ISOTOPE RATIO
ENANTIOMORPHS
MASS SPECTRA
METHADONE HYDROCHLORIDE
BIOCHEMICAL REACTION KINETICS
BLOOD PLASMA
PATIENTS
STEREOCHEMISTRY
URINE
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BLOOD
BODY FLUIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
HYDROGEN COMPOUNDS
KINETICS
MATERIALS
NARCOTICS
REACTION KINETICS
SPECTRA
WASTES
400103* - Radiometric & Radiochemical Procedures- (-1987)