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A sharp separation of total belladonna alkaloids (atropine, hyoscyamine, and scopolamine) from chlorpheniramine1 and phenylpropanolamine2 was effected by partition column chromatography which permitted the colorimetric determination of the total belladonna alkaloids. The column utilized a stationary phase of pH 7.0 buffer with moving phases of 1:1 cyclohexane-carbon tetrachloride for removal of the chlorpheniramine, and chloroform for the elution of the alkaloids. Phenylpropanolamine was retained on the column. The method was applied to pharmaceutical formulations containing the belladonna alkaloids in combination with chlorpheniramine maleate and phenylpropanolamine hydrochloride.

Available indicator extraction methods were inadequate for the determination of isopropamide iodide in the presence of amine bases. The substance was complexed with methyl orange in pH 10.2 buffer and extracted into chloroform. Re-extraction of the color into 1 N hydrochloric acid and its spectrophotometric determination gave quantitative results. Calibration curves for other short chain quaternary amines were determined and compared to a known solution of methyl orange. Agreement with the theoretical value was obtained down to tetra- n -propyl ammonium iodide. Application of the method to the determination of isopropamide iodide in a pharmaceutical preparation gave results ranging from 98.7 to 101.3 per cent of the theoretical amount present.

Atropine/hyoscyamine and scopolamine, in dosage forms in which the scopolamine represented less than 9% of the total belladonna alkaloids, were isolated as free bases from phenyl-propanolamine, chlorpheniramine, and interfering excipients by a series of pH- and solvent-controlled extractions and were quantitated by GLC. Homatropine was used as the internal standard. Precision and accuracy data are represented, along with assay results on three commercial capsule lots.

Differences in solubility and in rate of solubility from previously tested chemical lots were observed in a dimenhydrinate chemical evaluated by the tests and specifications in the official monograph. An impurity was isolated from the lot in question and was identified as 8-(2-diphenylmethoxy-N-methylethylamine)-1,3-dimethylxanthine based on spectral and elemental data.