UHPLC Quantitation Method and In vitro Studies of Two New Phthalimide Derivatives Planned to Treat Sickle Cell Disease

Background: Sickle cell disease is characterized by the occurrence of acute disability and progressive organ damage, and it is one of the most common and severe monogenic disorders around the world. Since hydroxycarbamide is the only drug approved by the Food and Drug Administration (FDA) to treat this disease, it is necessary to continue the development of new drug candidates to improve its treatment. Two of a series of phthalimide derivatives have shown great potential as a new drug candidate. Methods: Accordingly, a UHPLC quantitation method was developed and used to determine the chemical and plasma stability of these compounds. Their experimental log P values are presented here for the first time. Results: Method validation results were within appropriate limits for the application of UHPLC. The experimental log P was 2.56 for LAPDESF-SCD03 and 2.59 for LAPDESF-SCD04. The chemical stability of LAPDESF-SCD03 was better at pH 1.2, while for LAPDESF-SCD04, there was a significant reduction in drug at the 30-minute time point at pH 1.2 and 7.4. In the plasma hydrolysis study, LAPDESF-SCD03 showed a significant decay within 5 minutes, while LAPDESF-SCD04 was significantly lower than at time zero just in 15 min. Similar decay rate constants were observed for the two compounds. Conclusion: Both compounds have a stability profile that may be related to their proved effectiveness. (AU)