Abstract
With furylmethylketone isonicotinoylhydrazone (FKI) used as an example, factors affecting drug stability in various culture media and its implications on the in vitro activity tests have been studied. In buffer solution (pH 2-10), FKI was stable in the neutral pH and unstable in acidic and alkaline pH regions. It became evident that in culture media the degradative reaction was greatly influenced by medium components such as serum and amino acids. The rate of degradation was four to ten times more rapid than in buffer solutions and considerable amounts of isoniazid were released long before one could expect growth of test organisms in culture. Among the medium components tested, amino acids such as asparagine and glutamic acid exhibited a dominant effect and the data seemed to indicate non-protonated amino group as catalytic species. Suggestions are made relative to the significance of these observations for the in vitro evaluation of anti-bacterial agents.
