Exposure to ambient air causes degradation and decreased in vitro potency of buparvaquone and parvaquone

Buparvaquone and parvaquone are hydroxynaphthoquinone compounds commonly used to treat livestock infected with Theileria species such as T. parva and T. annulata. In many (sub)tropical regions, chromatic changes in medicines can result from extreme environmental conditions and improper drug storage or handling, raising the possibility of drug degradation and loss of potency. We evaluated the effects of UV light, elevated temperature, and atmospheric air on the stability and potency of both buparvaquone and parvaquone by using a combination of high performance liquid chromatography (HPLC) and a T. equi based in vitro parasite growth inhibition assay (to measure potency). Aliquots (1ml; 3 replicates per treatment) of each compound were subjected to a variety of treatments that varied in duration and intensity followed by HPLC and potency assays. Exposure to ambient air for 50 days was correlated with a significant loss of potency for both buparvaquone (4535%, P< 0.05) and parvaquone (247%, P< 0.05), while elevated temperature (37°C) and UV light exposure (24 h) had no significant impact (P> 0.05). The decrease in potency of both buparvaquone and parvaquone correlated with drug degradation (r = -0.74 and -0.88, respectively) as measured by HPLC. In practice, if there is headspace present in the vial, then ambient air will invariably enter the vial and contribute to degradation of these compounds. Such degradation may contribute to increasing drug resistance, economic losses for farmers, and animal welfare concerns for animals that are treated for Theileria infections.