Identification of 17 alpha,20 alpha-dihydroxyprogesterone in testicular extracts after incubation with ketoconazole.

The antifungal ketoconazole affects testosterone synthesis in dispersed rat testicular cells. In the presence of ketoconazole an accumulation of 17 alpha,20 alpha-dihydroxyprogesterone has been observed. This steroid was isolated from the testis of Wistar rats after a [4-14C]progesterone incorporation in the presence of ketoconazole. Its identification was achieved from the gas chromatographic/mass spectrometric analysis of the isolated radioactive fraction. A chemical derivatization of the fraction with butylboronic acid followed by mass spectrometric analysis confirmed the presence of 17 alpha,20 alpha-dihydroxyprogesterone.

Mass spectral investigation of the metabolites of lorcainide in man.

[3H] Lorcainide hydrochloride was administered orally to healthy male volunteers. About 97% of the total radioactivity was excreted in the urine and faeces within four days of its administration. The metabolites were purified by adsorption chromatography, liquid-liquid extraction, thin layer chromatography or by gas chromatography-mass spectrometry after silylation of the samples. When there was a sufficient amount available, the samples were submitted to a nuclear magnetic resonance analysis. The results were confirmed by comparison of spectral data obtained from the reference compounds. The major metabolites of lorcainide were formed by aromatic hydroxylation, O-methylation and oxidative N-dealkylation. The urinary phenolic metabolites were present both as free aglycons and conjugates.

In vitro and in vivo effects of the antimycotic drug ketoconazole on sterol synthesis.

Ketoconazole, an orally active antimycotic drug, is a potent inhibitor of ergosterol biosynthesis in Candida albicans when added to culture media which support yeast or mycelial growth or to cultures containing outgrown mycelium. This inhibition coincides with accumulation of sterols with a methyl group at C-14 and can thus be attributed to an interference with one of the reactions involved in the removal of the 14 alpha-methyl group of lanosterol. When administered to rats infected with C. albicans, ketocanazole also inhibits fungal synthesis of ergosterol. A six-times-higher dose is required to effect cholesterol synthesis by rat liver.

Structure of the major gangliosides from bovine thyroid.

After preparative isolation, the carbohydrate, long chain base, and fatty acid composition of the major gangliosides from bovine thyroid have been analyzed. The structures were elucidated by determining the molar ratio of the building blocks, permethylation analysis, and enzymatic degradation studies. The following structures are identified: N-Acetylneuraminyl(2,3)-galactosyl(1,4)glucosyl(1,1)ceramidie; N-glycolyneuraminyl(2,3)galactosyl(1,4)glucosyl(1,1)ceramide; galactosyl(1,3)N-acetylgalactosaminyl[(3,2)N-acetylneuraminyl](1,4)galactosyl(1,4)glucosyl(1,1)ceramide; fucosyl(1,2)galactosyl(1,3)N-acetylgalactosaminyl[(3,2)N-acetylneuraminyl](1,4)galactosyl(1,4)glucosyl(1,1)-ceramide. The structures were confirmed by direct inlet mass spectrometry of the permethylated gangliosides and the corresponding asialo derivatives. Structures are proposed for common ions in the different mass spectra.

In-vitro metabolism of etomidate by rat liver fractions.

(R)-(+)-etomidate and (S)-(-)-etomidate were found to be metabolized in-vitro by various rat liver homogenization fractions: the 16,000 g supernatant fraction caused a more intensive metabolic breakdown than the microsomal fraction; the 100,000 g supernatant fraction was only slightly active. The metabolism was somewhat more rapid and more extensive for the (R)-(+)-etomidate than for the (S)-(-)-isomer. For both isomers, a dose-dependence was observed: the smaller the substrate concentration, the smaller the relative amount of unmetabolized drug, and the more the rate of metabolic breakdown after a certain incubation time slowed down. Only minor qualitative differences between the metabolic pathways of the two isomers were observed. The main metabolic pathway for the in-vitro metabolism was the hydrolysis of the ethyl ester. Decarboxylation and oxidative N-dealkylation were also observed.