Spectrophotometric method for the determination of phenothiazines and its application to phenothiazine drugs

Abstract

A method for the spectrophotometric determination of four phenothiazines (promazine hydrochloride, mepazine hydrochloride, chlorpromazine hydrochloride and prochlorperazine maleate), based on the coloured compounds formed between the phenothiazines and molybdoarsenic acid, is described. The infrared and electron spin resonance spectra of these coloured compounds showed that the molybdoarsenic acid oxidises phenothiazines to a radical cation with which it subsequently forms the coloured compound. The method is simple and rapid. The influence of the substrates commonly employed as excipients with phenothiazine drugs was studied. The proposed method has been applied to the analysis of commercial phenothiazinecontaining preparations, the results of which are in good agreement with those obtained by the official method of the British Pharmacopoeia.During the past 25 years, interest in mental health and the continued introduction of new phenothiazine drugs have resulted in an extensive literature on the analysis of phenothiazines. The methods available for the determination of phenothiazines are all in some way unsatisf a~t o r y , l -~ and there is at present a great demand for a rapid, simple and accurate method for the routine quality control of phenothiazines. We therefore investigated the colour reaction between molybdoarsenic acid and four phenothiazines [promazine hydrochloride (PMH), mepazine hydrochloride (MH) , chlorpromazine hydrochloride (CPH) and prochlorperazine maleate (PCPM)]. The proposed method offers the advantages of simplicity, rapidity, reasonable sensitivity and a wide range of concentrations. Further, the reaction occurs at room temperature and without the need for extraction. Experimental ApparatusA Beckman, Model DB, spectrophotometer with matched 10-mm silica cells was used for absorbance measurements. A Perkin-Elmer, Model 257, infrared spectrophotometer and a Varian E-4 X-band electron spin resonance spectrometer were used for spectral analyses of the coloured compounds. ReagentsMolybdoarsenic acid was obtained from Doxa Laboratory, India. A 4% m/V aqueous solution was prepared.Stock solutions of PMH, MH, CPH and PCPM were prepared by dissolving the appropriate amount of sample in water, and were then standardised gra~imetrically.~ Working solutions were prepared as required by dilution. All other reagents were of analytical-reagent grade. Doubly distilled water was used throughout. Molybdoarsenic acid.Phenothiazines. ProcedureProcedure and preparation of calibration graph CPH or 155-1 180 pg of PCPM were transferred into a series of 25-ml calibrated flasks.Various aliquots containing 100-890 pg of PMH, 100-930 pg of MH, 140-1 115 pg of A

A Novel Spectrophotometric Determination of Some Phenothiazines Involving Iodine monochloride from Chloramine‐T with Iodine

“…The proposed method is economical, sensitive and the results are reproducible with a novel stability in the color of the phenothiazine solutions under the optimized experimental condition. The proposed method is unlike the earlier ones, which appear to have limitations regarding either sensitivity [43,44] or stability [45,46]. In addition, most of those reported methods require either extraction [47,48] or heating [79], but the proposed method involves neither critical reaction conditions nor tedious sample preparation.…”

“…There are quite a good number of reviews on the determination of phenothiazines [37Ϫ39], and more methods seem to follow [40Ϫ42]. Such interest on phenothiazines is not only due to their importance but also due to the fact that the reported methods appear to suffer from sensitivity [43,44] and/or stability [45,46], or require tedious extraction [47,48], heating [49Ϫ51] or cooling [52], they have a narrow range of detection [53,54] or employ concentrated sulfuric acid [55,56], which is a hazardous acid to handle [57].…”

Determination of Some Phenothiazines Compounds in Pharmaceuticals and Human Body Fluid by Electrocatalytic Oxidation at a Glassy Carbon Electrode Using Methylene Blue as a Mediator

“…Many methods have been reported for the individual determination of phenothiazines compounds, including spectrophotometry (Ramappa et al 1980;Livertoux et al 1981;Basavaiah et al 1998;El-Shabouri, 1985;Karpinska, 2000), (Gandhi et al 1984), HPLC (Stevenson et al 1981;Wallace et al 1981;Mehta, 1981), titrimetry (Walash et al 1983), and spectrofluorimetry (Zakhari et al 1985). With all these procedures, a prior extraction is required for the quantitation of these compounds in mixtures with other compounds or in complex matrices.…”

Ion-pair complex-based solvent extraction combined with chemiluminescence determination of chlorpromazine hydrochloride with luminol in reverse micelles

“…From a bioanalytical and clinical point of view, sensitive and accurate methods are needed to monitor chlorpromazine in pharmaceuticals and biological fluids for quality assurance in preparations and for obtaining optimum therapeutic concentrations. Although many methods have been reported for this purpose [1][2][3][4][5][6], the selective procedures require relatively extensive sample preparation and are time-consuming, while complicated instruments are used when high sensitivity is desired.…”