Stereospecific radioimmunoassay of alpha-l-acetylmethadol (LAAM)

A sensitive and specific radioimmunoassay has been developed which allows quantitation of picogram amounts of alpha-l-acetylmethadol (LAAM) in biological fluids without prior extraction. Antiserum was obtained from rabbits immunized with antigen prepared by conjugation of alpha-l-methadol hemisuccinate with thyroglobulin. The antiserum was stereospecific, distinguishing LAAM from its three stereoisomers. In addition, there was little cross-reaction in the assay by metabolites of LAAM and no interference with the assay by other narcotic analgesics. The sensitivity of the assay was 50 pg, requiring serum sample sizes as small as 10 microliters. The radioimmunoassay was used to determine serum concentrations of LAAM in five female dogs receiving i.v. injections of 2 mg/kg of LAAM. The decay of LAAM in serum appeared to be multiexponential, with a mean terminal half-life of 35 hr. The dogs were behaviorally depressed for at least 9 hr and hypothermic for at least 24 hr after injection. The persistence of these pharmacological effects was probably due to the slow elimination of LAAM and the presence of major metabolites which are pharmacologically active.