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

A spectrophotometric method is described for the rapid determination o f four thioxanthene derivatives, namely chlorprothixene, thiothixene, flupenthixol hydrochloride and clopenthixol hydrochloride. The method is based on measuring the first derivative spectrum (D1) of the oxidiz ed drug relative to a solution of the underivatized drug. At the wavel ength of maximum difference in first derivative (range 285-315 nm), on ly the oxidation products have an appreciable difference in first deri vative and the oxidizing agent has no absorbance. The oxidation produc ts (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 chloroprothixe ne, 2-20 mug ml-1 for clopenthixol hydrochloride, 2-24 mug ml-1 for th iothixene 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 excipie nts. The recoveries ranged from 99.7 +/- 1.3 to 100.2 +/- 1.5%. The va lidity of the method was tested by analysing synthetic samples of thio xanthenes and some dosage forms containing the drugs; the results were in accordance with those given by the official methods.