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Degradation of busulfan in aqueous solution
Abstract:
The influence of pH, phosphate buffer components and temperature on the degradation rate of busulfan was studied. The analysis was performed using gas chromatography with electron capture detection and reversed-phase liquid chromatography with radioactivity monitoring. The degradation rate of busulfan showed no pH dependence in the range pH 1.5-11 and increased at higher pH values. The degradation rate constant was 0.034 +/- 0.001 h(-1) (S.E.M.) for the degradation of busulfan in pure water and 0.45 +/- 0.01 h(-1)M(-1) (S.E.M.) for the reaction of busulfan with the hydroxide ion at 37 degrees C. The reactivity of HPO(4)(-2) was six times higher than the reactivity of H(2)PO(4)(-1) towards busulfan. The hydrolysis products were identified as tetrahydrofuran and methanesulphonic acid by nuclear magnetic resonance spectroscopy.
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