Identification of canine urinary metabolites of the antiprotozoal agent 3a,4,5,6,7,7a-hexahydro-3-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,2-benzisoxazole .

Metabolite fractions from the urine of a dog dosed with 3a,4,5,6,7a-hexahydro-3-(1-methyl-5-nitro-1H-imidazol-2-yl)-1,2-benzisoxazole (MK-0436) were obtained by the use of high-performance liquid chromatography. These fractions were of suitable purity for structural elucidation. Data obtained by mass spectrometry and NMR spectroscopy allowed the identification of seven major metabolites of this drug. Biotransformation in each case involved hydroxylation (mono or di) of the hexahydrobenzisoxazole ring.

Stability-indicating analysis of injectable estrogen-androgen combinations in formulations containing corn oil.

A method was developed for the analysis of testosterone 17-enanthate 3-benzilic acid hydrazone, 17-beta-estradiol 3,17-dienanthate, and estradiol benzoate combinations dissolved in an oily vehicle. Testosterone 17-enanthate 3-benzilic acid hydrazone was separated from the other drugs and vehicle components by chromatography on an acetonitrile-infusorial earth column followed by quantitation using UV spectroscopy. The estradiol esters were separated from the oil by an additional chromatographic step using a heptane-silanized infusorial earth column prior to quantitation by GLC. Subjecting formulations to elevated temperatures resulted in detectable losses for testosterone 17-enanthate 3-benzilic acid hydrazone and 17-beta-estradiol 3,17-dienanthate. For both drugs, degradation was due to hydroxysis; the degradation products, testosterone 17-enanthate and 17-beta-estradiol 17-enanthate, did not interfere with the intact drug determination. Methods also were developed to estimate degradation product levels in the formulation.

In vitro O-demethylation of the psychotomimetic amine, 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane.

The possible relationship between metabolism and psychotomimetic activity among the methoxylated 1-phenyl-2-aminopropanes led to our investigation of the in vitro O-demethylation of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (1, DOM, STP). Employing a sensitive and highly selective stable isotope dilution assay, we observed that rabbit liver homogenates biotransform the amine 1 to its 2-O-demethyl, 5-O-demethyl, and bis (O-demethyl) metabolite metabolites. Both monophenolic metabolites are enriched in their S enantiomers. The bis(O-demethyl) metabolite has structural, chemical, and electrochemical similarites to the sympatholytic agent "6-hydroxydopamine". The possible significance of metabolic O-demethylation in terms of the psychotomimetic properties of amine 1 is discussed.