A CHEMICAL-STABILITY STUDY OF PROGUANIL HYDROCHLORIDE

A stability-indicating assay method is described for proguanil based on reversed-phase ion-pairing HPLC. Using this method a study of the stability of proguanil in solution is made. In solution, proguanil decomposes by a first-order reaction. It is shown that the major decomposition product is 4-chloroaniline and that two other minor products can be detected but not identified. First-order rate constants over the temperature range 40-90°C are determined and an activation energy of 90.8 kJ mol-1 derived. The log k-pH profile is determined and indicates maximum stability in the range pH 6-8. From the magnitudes of the rate constants obtained, it is evident that proguanil is a very stable drug in solution. The effect of ultraviolet radiation on proguanil is to produce the same decomposition products. The effects of thermal stress and ultraviolet on a tablet formulation of proguanil (Paludrine *) are also studied and these further confirm the stability of this compound to both thermal and photochemical stress. © 1990.