Rapid, precise, accurate and specific high performance liquid chromatographic and derivative ratio spectra spectrophotometry procedures are described for the simultaneous analysis of chlorpheniramine maleate and phenylephrine hydrochloride in combined pharmaceutical dosage forms. The chromatographic methods were standardised using a LiChrosorb RP-C-18 column (5 mu m, 20 cm x 4.6 mm), UV detection at 269.0 nm and mobile phases consisting of methanol/phosphate buffer (50 ml 0.2 M monobasic potassium phosphate (KH2PO4) + 34.7 ml 0.2 M NaOH; 70:30, apparent pH 7.2). Using derivative ratio spectra spectrophotometry, the amplitudes in the first derivative of the ratio spectra at 238.9 and 280.0 nm were selected to determine chlorpheniramine maleate and phenylephrine hydrochloride in the mixture. Commercial nasal drops and laboratory-prepared mixtures containing both drugs in different proportions were assayed using the methods developed. Both methods showed good linearity, precision and reproducibility. (C) 1998 Elsevier Science S.A. All rights reserved.