URINARY-EXCRETION OF CHLORPHENIRAMINE AND PSEUDOEPHEDRINE IN HUMANS

A specific high‐pressure liquid chromatographic method for the determination of chlorpheniramine and pseudoephedrine in urine was developed and applied in a urinary excretion study of normal healthy subjects who received a sustained‐release dosage form containing 8 mg of chlorpheniramine maleate and 120 mg of pseudoephedrine hydro‐chloride. Five subjects received one dose on Day 1, followed by multiple dosing every 12 hr for 7 days without ammonium chloride administration. Four subjects received one dose of the sustained‐release dosage form together with ammonium chloride. Urine samples were collected during the 1st day and at steady state. The method is specific and simultaneously determines chlorpheniramine, two metabolites (mono‐ and didesmethylchlorpheniramine), pseudoephedrine, and norpseudoephndrine. The assay recovery was >97% (0.06‐3 μg/ml) for chlor‐pheniramine maleate and >98% (1.5‐75 μ/ml) for pseudoephedrine hydrochloride. Excretion of chlorpheniramine and its two metabolites in urine was enhanced after ammonium chloride administration. At steady state, a change in urine pH from 5.69 to 6.46 resulted in more than a 25% decrease in chlorpheniramine and monodesmethylchlorpheniramine excretion. In spite of expected changes in its biological half life, the overall amount of unchanged pseudoephedrine excreted in urine was not affected by urine pH, presumably because it is primarily excreted in urine as intact drug. Copyright © 1979 Wiley‐Liss, Inc., A Wiley Company