Determination of chlorpromazine and its sulphoxide in pharmaceutical dosage forms by third-order derivative ultraviolet spectroscopy.

In pharmaceutical dosage forms, interference in the UV spectra of analytes by other UV-absorbing solutes leads to a requirement for the development of procedures with greater specificity. One method used to address this problem is the technique of derivative spectroscopy, where the composite spectrum is transformed to the second or higher derivative in the wavelength domain. This paper reports the novel application of this technique to the determination of a phenothiazine (chlorpromazine) and its sulphoxide impurity in various pharmaceutical dosage forms.A systematic approach developed for optimisation of the derivative order, graphical measurement and instrumental conditions led to the adoption of third-order derivative spectroscopy as a method with suitable precision and selectivity for the determination of the phenothiazines. Both the parent compound and the sulphoxide impurity can be assayed in dosage forms by measurement of the amplitudes of, respectively, the positive peak at 259 nm with respect to the negative peak at 267 nm, and the positive peak at 350 nm with respect to the negative peak at 361 nm. A new notation for denoting these amplitude measures is proposed, viz., 3D259,267 and 3D350,361, respectively. By comparison with an independent referee method based on reversed-phase HPLC, the proposed method and the referee method gave statistically similar results for the determination of chlorpromazine and its sulphoxide in injectables, tablets and syrups. The figures of merit for the proposed assays are described in terms of response linearity, 95% confidence limits, relative standard deviation, recovery data and correlation coefficients. It is suggested that similar methodology should be applicable to the analysis of other members of the phenothiazine class of compounds.