DIFFERENCE SPECTROPHOTOMETRIC DETERMINATION OF SOME PHARMACEUTICALLY IMPORTANT THIOXANTHENE DERIVATIVES IN DOSAGE FORMS

A spectrophotometric method is described for the rapid determination of four thioxanthene derivatives, namely chlorprothixene, thiothixene, flupenthixol hydrochloride and clopenthixol hydrochloride. The method is based on measuring the first derivative spectrum (D1) of the oxidized drug relative to a solution of the underivatized drug. At the wavelength of maximum difference in first derivative (range 285-315 nm), only the oxidation products have an appreciable difference in first derivative and the oxidizing agent has no absorbance. The oxidation products (assumed to be the thioxanthone sulphoxides) are formed rapidly at room temperature by the addition of peroxyacetic acid, prepared by the slow reaction of hydrogen peroxide and glacial acetic acid. The first derivative of the absorbance is proportional to the concentration of the drugs in solution over the ranges 2-14 mug ml-1 for chloroprothixene, 2-20 mug ml-1 for clopenthixol hydrochloride, 2-24 mug ml-1 for thiothixene and 4-40 mug ml-1 for flupenthixol hydrochloride. The method is specific for the intact drug and can be adopted in the presence of oxidative and photochemical decomposition products and tablet excipients. The recoveries ranged from 99.7 +/- 1.3 to 100.2 +/- 1.5%. The validity of the method was tested by analysing synthetic samples of thioxanthenes and some dosage forms containing the drugs; the results were in accordance with those given by the official methods.