Decomposition of etoposide in aqueous-organic solutions and separation of its degradation products by HPLC
Abstract
The purpose of this study is optimization of HPLC analysis conditions for etoposide and its decomposition products and application of the mobile phase based on volatile, transparent in the short wavelength ultraviolet region of the spectrum components to approach the way to unify the chromatography analysis.
We determined kinetic parameters for etoposide decomposition in the alkaline medium. We have studied for the first time the effect of acetonitrile and dimethyl sulfoxide on the rate of etoposide decomposition in the alkaline aqueous-organic solution. We showed that organic solvents inhibit the degradation due to the changed dielectric constant of the medium. The effect of dimethyl sulfoxide on degradation and peak shape is much weaker, because of its higher dielectric constant and polarity compared to acetonitrile.
The separation conditions of etoposide and its decomposition products by means of reverse-phase HPLC are selected. We compared the retention time received for degradation products at different pH of the mobile phase with the data from literature, and the assumption is made about the chemical nature of the decomposition products of etoposide in the alkaline medium. We showed the possibilities of use of mobile phase containing water, acetonitrile, perchloric acid and ammonia to increase sensitivity of detection. This approach is perspective for other drugs of different chemical nature.
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