Development and optimization of HPLC method for determination of peroxide impurities in pharmaceutical excipients

The chemical stability of drugs can be affected by impurities that occur in commonly used excipients. Hydroperoxides are common trace impurities, especially in polymeric excipients, which can cause oxidative degradation of drugs. Several methods for the quantification of trace levels of hydroperoxides (hydrogen peroxide and organic hydroperoxides) are described in the literature. However, there are few studies dealing with the quantification of trace levels (ppm) of hydroperoxides in drug excipients. The goal of this thesis was the development and optimization of an HPLC method with UV detection for the determination of hydroperoxides in drug excipients, based on methods already described in the literature. The developed HPLC method is based on the determination of triphenylphosphine oxide as a product of the rapid and quantitative reaction of triphenylphosphine with hydroperoxides. Method development also included optimization of sample preparation prior to HPLC analysis. During the experimental work, the influence of individual experimental parameters and sample preparation conditions on the determination of hydroperoxides was determined. The optimized HPLC method used a Kinetex F5 column (100 × 4,6 mm, 2,6 µm) and a mixture of water and acetonitrile as the mobile phase with gradient elution. As..