Determination of sodium levothyroxine in bulk, tablet, and injection formulations by high-performance liquid chromatography.

Sodium levothyroxine was determined in bulk drugs, tablets, and injections by high-performance liquid chromatography (HPLC). Levothyroxine was separated from excipients and impurities on a 10-microns cyanoalkyl column using an acetonitrile-water-phosphoric acid mobile phase. The HPLC method is shown to be linear, accurate, and precise, and the results obtained by the HPLC and USP XX methods are compared.

Liquid chromatographic determination of prednisolone in tablets and bulk drugs: interlaboratory study.

A normal phase liquid chromatographic (LC) method for the determination of prednisolone in tablets and bulk drugs was studied by 7 analysts. An LC system, consisting of a methanol-water-ethylene dichloride-acetic acid mobile phase and a silica column, was used to analyze bulk drugs, individual tablets, and composite samples. Analysts were supplied with 16 samples, including simulated formulations, composites of commercial tablets, intact tablets, and bulk drug substances. Results agreed with those obtained by the author. The coefficients of variation of the analysts' results ranged from 1.34% for bulk drugs to 2.14% for tablet composites. The LC method is suggested as an alternative to the official AOAC and USP XX blue tetrazolium colorimetric methods.

Decomposition of aminophylline in suppository formulations.

An aminophylline suppository product, when stored at room temperature, was found to be deficient in ethylenediamine content by the USP XIX assay and by a specific method for primary amines. The product also had a melting point that was considerably higher than body temperature. An accelerated decomposition experiment, conducted on normal suppositories of identical original composition, yielded a product refractory at steam bath temperatures and containing no ethylenediamine measurable by the USP assay. The suppositories from both the original sample and the decomposition experiment contained considerable amounts of a white material, which melted at similar to or approximately 150 degrees and which consisted of the diamide products formed by the reaction of ethylenediamine and the fatty acids present in coconut and palm kernel oils. The results, which confirmed the work of Cieszynski, showed that the ethylenediamine constituent of aminophylline can react with suppository base materials to produce insoluble amide decomposition products.

High-performance liquid chromatographic separation and identification of epimeric 17-ketone impurities in commercial sample of dexamethasone sodium phosphate.

A commercial sample of dexamethasone sodium phosphate solution for injection was found to contain 56% of the label concentration and to be extensively contaminated (approximately 50%) with a white insoluble solid, which was identified as a mixture of the 16 alpha- and 16 beta-methyl epimers of 9-fluoro-11 beta-hydroxy-16-methylandrosta-1,4-diene-3,17-dione. High-performance liquid chromatography (HPLC) was used to separate, identify, and quantitate these epimers and to determine their presence in commercial samples. One epimer was identified by HPLC comparison with a synthesized specimen of 9-fluoro-11 beta-hydroxy-16 alpha-methylan-drosta-1,4-diene-3,17-dione. The second peak was identified as the 16 beta-epimer by epimerization of the synthesized alpha-component with alkali to obtain a product whose chromatogram matched that of the impurity. These conclusions are supported by data obtained by IR and UV spectrophotometry, TLC, and the blue tetrazolium test.

Collaborative study of a semiautomated method for the analysis of prednisolone and prednisone tablets.

A semiautomated colorimetric method for the determination of prednisolone and prednisone was collaboratively studied by 6 collaborators. In the method, an alcoholic solution of the drug is extracted with chloroform and the extract is reacted with tetramethylammonium hydroxide and blue tetrazolium; the absorbance of the resulting color is read at 525 nm. Collaborators were supplied with 4 composites of tablets of different dosage levels, 2 containing prednisolone and 2 containing prednisone. Results agreed with those obtained by the author using the USP total steroid assay method. The coefficients of variation of the individual collaborator's results for prednisolone and prednisone ranged from 0.54 to 2.38 and from 0.34 to 2.19%, respectively. This method has been adopted as official first action.