[On the problem of dimethylnitrosamine formation from tetracycline-derivatives by nitrosation reaction in acidic medium (author's transl)]. / Zur Frage der Bildung von Dimethylnitrosamin aus Tetracyclin-Derivaten bei der Nitrosierung in saurer Lösung.

ABSTRACT

The hydrochlorides from tetracycline and six tetracycline derivatives -- 7-dimethylamino-6-des-methyl-6-desoxytetracycline [minocycline], 7-chlorotetracycline [chlorotetracycline], 7-chloro-anhydrotetracycline [anhydrochlorotetracycline, 7-chloro-6-desmethyltetracycline [demethylchlorotetracycline], 5-hydroxytetracycline [oxytetracycline] and 6-desoxy-5-hydroxytetracycline [doxycycline] -- were reacted with different amounts of sodium nitrite at 37 degrees C for two hours in aqueous buffer solutions at pH 2 and 4. Dimethylnitrosamine formation was confirmed by gas-liquid chromatography and by combined gas-liquid chromatography/mass-spectrometry from minocycline, doxycycline, oxytetracycline and anhydrochlorotetracycline. Dimethylnitrosamine formation from minocycline and doxycycline was blocked by ascorbic acid. The catalytic effect of sodium thiocyanate for the dimethylnitrosamine formation from minocycline and nitrite was investigated. The different reactivity of the investigated tetracycline derivatives towards nitrite in acidic solutions is discussed by stereochemical considerations in connection with the formation of hydrogen bridge linkages. This hypothesis was confirmed by dimethylnitrosamine formation from anhydrochlorotetracycline and sodium nitrite at pH 2.