326 AHalyst, May, 1968, Vol. 93, $$. 32f3-327 Spectrophotometric Determination of Carbinoxamine Maleate in Tablets containing Caffeine, Sulphamethoxypyridazine and Alginic Acid BY L. MOSCONI (Luborutori GZuxo S.P.A ., Verona, Italy) An ion-exchange chromatographic technique is described for a spectro- photometric determination of carbinoxamine maleate in the presence of caffeine and sulphamethoxypyridazine. A modified procedure is developed for tablets containing alginic acid. IN addition to methods hitherto proposed, which include non-aqueous titration,l a fluorimetric method2 and a colorimetric assay with bromocresol green: the spectrophotometric deter- mination of carbinoxamine described in this paper has proved especially useful for pharma- ceutical tablets containing analytically similar substances such as caffeine and sulphamethoxy- pyridazine. Clearly, a spectrophotometric procedure is applicable only if the carbinoxamine is previously separated from interfering substances.This is achieved by chromatography of an aqueous solution on a weakly acidic ion-exchange cellulose, on which carbinoxamine is retained; interfering compounds are not held and can be completely separated by elution. The carbinoxamine is then eluted as the hydrochloride with 0-5 N hydrochloric acid. If alginic acid, a widely used disintegrating agent, is present, the procedure needs modification as alginic acid absorbs carbinoxamine from aqueous solution. EXPERIMENTAL REAGENTS- Sodium chloride, 0.5 M. Sodium hydroxide, 3 N. Hydrochloric acid, 0-5 N. Chloroform. Carboxymethylcellulose, CM 11 Whatmart.PREPARATION OF THE COLUMN- Make a slurry of 1 g of carboxymethylcellulose with about 10 ml of 0.5 N hydrochloric acid and transfer it quantitatively to a glass column (1 cm i.d. x 25 cm) between two plugs of glass-wool. Wash the column with distilled water until the effluent is neutral. PROCEDURE- (1) Alginic acid absent-Prepare an aqueous solution of the sample, so that the car- binoxamine concentration is about 0404 per cent. w/v (concentrations of caffeine and sulphamethoxypyridazine may be up to twenty times greater). If necessary, filter the solution through a sintered glass filter, then pass 10.0ml of the solution through the column. Discard the effluent, wash the column with 100 ml of distilled water and elute with 0.5 N hydrochloric acid; collect 20 ml of the eluate in a graduated flask.Measure the extinction in a 1-cm cell against 0.5 N hydrochloric acid at 264 mp, and calculate the carbinoxamine content of the sample. The Ei2m value for carbinoxamine is 245 at 264mp. 0 SAC and the author.MOSCONI 327 (2) Alginic acid @resent-Prepare a solution of the sample in 0-5 M sodium chloride, so that the carbinoxamine concentration is about 0.02 per cent. w/v. Filter through a sintered glass filter, then transfer 10-0 ml of the filtrate into a separating funnel. Add 2 ml of 3 N sodium hydroxide and extract five times with 20-ml portions of chloroform. Filter the extracts through a layer of anhydrous sodium sulphate, which is supported on a plug of absorbent cotton-wool, and evaporate the filtrate on a boiling water bath, finally evaporating it to dryness under nitrogen. Dissolve the residue in hot distilled water and transfer it quantitatively into a 50-ml graduated flask; cool and dilute to volume.Proceed as in Procedure (1) from “pass 10.0 ml of the solution through the column. . . .” DISCUSSION The ultraviolet absorption curve of carbinoxamine in 0.5 N hydrochloric acid shows a maximum at about 264mp; the Ei:m value determined experimentally at this maximum is 245. Solutions follow the Lambert -Beer law over a range of concentrations from O W 0 4 to 0.004 per cent. (optical densities from about 0-1 to l o o ) , and the shape of the peak is unaffected by chromatography on carboxymethylcellulose. Table I shows the effects of caffeine and sulphamethoxypyridazine on the determination of carbinoxamine without, and after, chromatography. TABLE I RECOVERY OF CARBINOXAMINE FROM AQUEOUS SOLUTIONS* Purification treatment 7 - 3 Extraction and Other substances added None Chromatography chromatography None .... .. . . 0,490 0.490 0.485 Caffeine .. .. .. .. >3 0.490 f 0.006 - Sulphamethoxypy-ridazine . . >3 0.490 f 0.006 - Alginic acid? . . .. . . 0.120 - 0.120 Alginic acid+ sodium chloride, 0.6 M? . . . . 0.490 - 0-486 hydrochloric acid. * Results expressed as extinction values of a 0*0020 per cent. solution in 0.6~ t Solution centrifuged. The sorption of carbinoxamine by alginic acid in aqueous solution may be prevented by adding sodium chloride, but such a solution is clearly unsuitable for chromatography. Under alkaline conditions, carbinoxamine can be extracted quantitatively with chloroform ; the solution, when evaporated to dryness, yields a residue free from salt and alginate, and is suitable for ion-exchange chromatography. Results in Table I show satisfactory recovery by this method in the presence of alginate. Over-all recovery on formulated products was 99 2 per cent. I thank Mr. W. H. C. Shaw for his helpful advice. REFERENCES 1. 2. 3. Meites, L., Editor, “Handbook of Analytical Chemistry,’’ First Edition, McGraw-Hill Book Co. Inc., New York, Toronto and London, 1963, Section 13, p. 201. Jensen, R. E., and Haurn, R. T., J . Phurm. Sci., 1964, 53, 836. Tanaka, I., Otani, S., Nakayashiki, J., and Fujita, S., Yukuzuiguku [Arch. Pruct. Pharm.], 1964, 24, 303; Chem. Abstr., 1966, 63, 1664a. Received November 8th, 1967