Abstract
A method for the determination of methadone is described which is applicable to tissues, feces and urine. The method is based on liberation of methadone by disintegration of tissue with strong alkali; isolation of basic compounds soluble in ether; determination of phenyl radicals in the fraction containing organic bases by nitration and color development with ethylmethyl ketone. Reproducibility is 5 per cent; sensitivity 1 microgm. of methadone.
Methadone is slowly removed from the site of the subcutaneous injection.
About 50 per cent to 60 per cent of the injected dose disappears from the body of the rat within five hours. Excretion in feces and urine accounts for only a small fraction of the drug disappearing.
The distribution of the drug in normal rats at various time intervals after injection has been determined. Brain, the assumed site of the analgesic action, contains the smallest fraction of the injected methadone. Concentration in the brain and analgesic action have been compared.
Liver slices destroy methadone aerobically.
The distribution of the drug in rats tolerant to a dose of 15 mgm./kgm. has been compared to the distribution of a similar dose in the normal animal. Certain differences in distribution have been observed and their significance has been discussed.
Liver slices from animals tolerant to methadone destroy methadone at approximately the same rate as slices from normal animals.
Footnotes
- Received January 5, 1950.
- 1950 by The American Society for Pharmacology and Experimental Therapeutics
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