Epimerization of erythromycin derivatives.

Dirithromycin (3) isomerizes upon dissolution in different solvents. From X-ray analysis of V-T 108, an analogue of dirithromycin, and comparative 1H and 13C NMR, and MS data, the isomer of dirithromycin was confirmed to be the C-16-(S)-epimer. The ratio of the two epimers at equilibrium conditions was approximately 8:2 (R/S) in methanol at room temperature.

Kinetic and analytic investigations on the formation of N-nitroso-N-methyl-N-cyclohexylamine from bromhexine and nitrite.

Bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammoniumhydr ochloride) forms N-nitroso-N-methyl-N-cyclohexylamine (NMCA) under the conditions of the WHO Nitrosation Assay Procedure (NAP-test). The formation kinetics of this compound was investigated. The formation of NMCA depends on the square of the nitrite concentration.

Lack of detectable N-nitroso-N-methyl-N-cyclohexylamine in humans after administration of bromhexine.

The possible formation of N-nitroso-N-methyl-N-cyclohexylamine (NMCA) from the drug bromhexine (N-methyl-N-cyclohexyl-(2-amino-3,5-dibromobenzyl)-ammonium hydrochloride) and nitrite was investigated in humans using three different approaches: 1. analysis on metabolites of NMCA in human urine; 2. analysis on NMCA in human gastric juice; 3.