Study of Oxyclozanide's Innate Stability Coupled with the Assessment of its Aquatic Photo-Transformation Using a Validated Isocratic HPLC Method.

Abstract

Background: Oxyclozanide (OXY) is a veterinary medicine used for control of fascioliasis in farm animals. Literature review shows absence of sufficient information regarding its stability. Such information is important as it affects many stages of a drug's life cycle, from pharmaceutical manufacturing to its environmental fate understanding of the degradation of the drug once it is placed in the environment. Objective: An HPLC method was developed to address the impact of different stress conditions on OXY's stability. Methods: OXY's stability was investigated by exposure to forced acid and alkaline hydrolysis, thermal, oxidative and photolytic degradation, which are different stress conditions applied to the forced degradation study. Separation was performed on Eurosphere C18 analytical column (125 × 4.6 mm, 5 μm particle size) using 50 mM sodium acetate trihydrate (pH 4.5) and acetonitrile (50:50, v/v) as mobile phase and UV detection at 254 nm. A photolytic kinetics study was conducted by monitoring OXY photolysis under monochromatic and polychromatic light sources (UV lamp at 366 nm and natural sunlight) in aqueous buffers of different pHs (5, 7, and 9). LC-MS was used to identify the major photolytic degradate. Results: OXY was quantified over a concentration range of 1-80 μg/mL with mean recovery of 99.32 ± 1.80%. The drug was susceptible to oxidative and photolytic degradation. The photolytic kinetics were pH dependent. The LC-MS result supported photo-dehalogenation degradation mechanism. Conclusions: The developed method could be used in OXY stability testing. The results of the photolytic kinetics study can address OXY aquatic photo-transformation, thereby predicting its environmental fate and risks imposed on the ecosystem. Highlights: An HPLC method was developed for monitoring OXY degradation behavior and studying its photolytic kinetics with identification of its photodegradate.