Determination of pKa and forced degradation of the indoloquinoline antimalarial compound cryptolepine hydrochloride

Abstract

The study was aimed at determining the acid dissociation constant of cryptolepine hydrochloride and its degradation under stressed conditions. The pKa was determined using buffers in the pH range 10.4–11.6 by spectrophotometry at controlled measurement temperature (20 ± 0.5°C). The stability of the compound was investigated under various stressed conditions including neutral, acid, alkaline, light, dry heat and oxidation at different temperatures. Degradation products were analysed by HPLC. The calculated pKa values (uncorrected and corrected for ionic strength) were 11.09 ± 0.03 and 10.99 ± 0.05, respectively. A graphical approach yielded an uncorrected pKa value of 11.07. Degradation of the compound in water, 0.1 M HCl, 0.1 M NaOH and 3% hydrogen peroxide followed a first order reaction. With proper temperature control and maintenance of uniform ionic strength, a reproducible pKa of cryptolepine is obtainable by spectrophotometry. The compound was found to be highly susceptible to oxidation and relatively stable in neutral and acidic conditions but less so in a basic medium. There were no significant changes in concentration of samples exposed to light and dry heat at 60°C over the study period.

Keywords::

• pKa determination
• ionization constant
• forced degradation
• cryptolepine
• malaria
• rate constant
• spectrophotometry