Sensitive high performance liquid chromatographic method for the determination of proguanil and its metabolites, cycloguanil and 4-chlorophenylbiguanide in biological fluids

A new simple, sensitive, cost-effective and reproducible high performance liquid chromatographic (HPLC) method for the determination of proguanil (PG) and its metabolites, cycloguanil (CG) and 4-chlorophenylbiguanide (4-CPB) in urine and plasma is described. The extraction procedure is a simple three-step process that has eliminated the need for costly extraction and evaporation equipment. The mobile phase consisted largely of buffer, making the method cheap to run. The calibration plots were linear over the concentration range up to 3.0 &#181g/ml PG, CG and 4-CPB in urine and concentration range up to 1000 ng/ml in plasma. The correlation coefficients (r) were of the order of 0.99 and above for PG and 4-CPB and 0.98 for CG. The ion pair method was carried out on a 5 &#181 reversed-phase C-18 column, using perchlorate ion as the counter ion and ultra violet detection at 254 nm. The method was reproducible with coefficient of variation for PG, CG and 4-CPB, being less than 10% in urine and plasma. PG was well resolved from its metabolites, CG and 4-CPB, and the internal standard, pyrimethamine. The limit of detection of PG was 10 ng/ml and the recovery was greater than 90% in urine and plasma. The analytical method therefore, exhibits good precision and sensitivity and is one of the few methods that can detect PG and the two metabolites CG and 4-CPB. The analytical method developed in this study was used to determine PG bioavailability after rectal administration in humans. Key words: Proguanil, HPLC, metabolites, biological fluids.African Journal of Biotechnology Vol. 4 (8), pp. 856-56

The efficacy of urine data in comparative bioavailability of proguanil after oral and rectal administration in man

The bioavailability of proguanil formulated as suppository, was compared to the tablet formulation in a bid to evaluate the utility of the suppository dosage form as means of administering proguanil in children and high-risk groups, such as sickle cell patients, who may not tolerate oral route of administration. The study was a completely randomized cross over involving administration of 200 mg of proguanil suppository and tablet to twelve healthy volunteers. Biological fluids such as urine and blood were collected before and at predetermined time intervals following administration of the drug. The biological samples were analyzed for the unchanged proguanil using an earlier reported method. The relative bioavailability of proguanil suppository as compared to the tablet dosage form was found to be about 61% from both urine and plasma data. The findings showed for the first time that proguanil suppository could be sufficiently bioavailable and may therefore be useful in chemoprophylaxis of malaria in sickle cell patients and children, particularly under such conditions that made oral route become impracticable.Key words: Proguanil, tablets, suppositories, plasma and urine data, bioavailability

The efficacy of urine data in comparative bioavailability of proguanil after oral and rectal administration in man

The bioavailability of proguanil formulated as suppository, was compared to the tablet formulation in a bid to evaluate the utility of the suppository dosage form as means of administering proguanil in children and high-risk groups, such as sickle cell patients, who may not tolerate oral route of administration. The study was a completely randomized cross over involving administration of 200 mg of proguanil suppository and tablet to twelve healthy volunteers. Biological fluids such as urine and blood were collected before and at predetermined time intervals following administration of the drug. The biological samples were analyzed for the unchanged proguanil using an earlier reported method. The relative bioavailability of proguanil suppository as compared to the tablet dosage form was found to be about 61% from both urine and plasma data. The findings showed for the first time that proguanil suppository could be sufficiently bioavailable and may therefore be useful in chemoprophylaxis of malaria in sickle cell patients and children, particularly under such conditions that made oral route become impracticable