Derivative spectrophotometric and high performance liquid chromatographic methods, for the determination of the centrally acting cough supressant clobutinol hydrochloride in syrups and drops have been developed. Spectrophotometrically clobutinol was determined by the measurement of its first ( 1 D) and second ( 2 D) derivative amplitudes at 277 and 275 nm. The aqueous acidic and alcoholic solutions obeyed Beer's law in the concentration range of 31.4-219.5 and 34.9-157.0 µg/ml measurements respectively. A liquid chromatographic assay has been also developed for the determination of clobutinol in the presence of other pharmaceutical compounds in the same pharmaceutical formulations. A reversed phase column Alltech (Lichrosorb 5 µm 250 × 4.6 mm id) was used with a mobile phase containing ammonium acetate buffer 0.05 M, methanol and CH 3 CN, 22:60:18 adjusted to pH 3.34 with acetic acid at a flow rate of 1 ml min −1 . The retention behaviour of clobutinol as function of both pH and mobile phase composition was investigated. Quantitation was achieved with UV detection at 267 nm based on peak height. Beer's law was obeyed in a concentration range of 34.7-243.0 µg/ml. For the described methods the regression line equations were derived with a correlation coefficient better than 0.9973. The proposed procedures were successfully applied to the determination of clobutinol hydrochloride in commercial pharmaceutical formulations and in placebo syrup prepared in the laboratory with good accuracy and precision. No significant differences were found between the results obtained both by the HPLC and derivative procedures.