High Performance Liquid Chromatographic Analysis of Proguanil and its Metabolites in Biological Fluids.

Ilori, Oluseyi Bamidele (1986)


Proguanil (Paludrine(R)) is widely used in the prophylaxis of malaria. A sensitive high performance liquid chromatographic (hplc) method was developed for the analysis of proguanil and its two known metabolites, cycloguanil and 4-chlorophenylbiguanide in urine and plasma. This method, an ion-pair technique] involved the use of a C18 reversed phase column (5µm) through which is pumped at 1ml/min a solvent system of methanol: 0.5% ammonium acetate (1:1) containing 50mM/L perchloric acid to provide the counter-ion. Detection was at fixed wave-length of 254nm. The minimum detectable concentration for the three compounds was 50ng/ml. Proguanil had a capacity factor of 2.82 in the solvent system. The coefficient of variation, a measure of precision of the analytical method was less than 10% for the drug. The recovery of proguanil from the biological fluids was greater than 70%. The method was applied for the determination of proguanil and its metabolites in urine samples of four apparently healthy volunteers following oral administration of 100mg proguanil. Urine samples were collected for 7 days. The total drug excreted was 61±15% (± S.D).The unchanged drug accounted for about 76% of the amount excreted while cycloguanil and 4-chlorophenylbiguanide accounted for 12% each. The maximum urinary excretion rate was attained in the third hour in all the volunteers. The mean elimination half life (t1/2) of the drug was calculated to be 15.2 ± 1.3 hr (± S.D).