Abstract
There are many halogen-containing compounds, which were classified into three groups tentatively, that is, the drugs containing 1) ionic halogens, 2) non-ionic halogens, and 3) both ionic and non-ionic single halogens. Quantitative determination of halogens in drugs were carried out by atomic absorption spectrophotometry and satisfactory results were obtained.
The recommended procedures are as follows: Samples containing ionic halogens, such as, guanidine hydrochloride and propantheline bromide, were dissolved in water. It was found that desirable concentrations of the sample solutions were 25 μg/ml for Cl-containing drugs, and 100 μg/ml for both Br-and I-containing drugs for the measurements, respectively.
Then, proper amounts of the sample solution (14 ml) was made acidic with nitric acid, being followed by the addition of 5 m/ of 100 μg/ml silver nitrate solution, and the resultant solution was warmed on a water-bath for 1 min. It was kept standing for 30 min at a room-temperature, the precipitates were filtered off and the filtrate was diluted to 100 ml with water, then excess amounts of silver were determined by atomic absorption spectrophotometer. Samples containing non-ionic halogens, such as bromisovalum and iodoform, were fused with metallic sodium of 1020 times as much as the samples taken and after the decomposition of excess metallic sodium unreacted with water, the residues were filtered off and the filtrate was used as a sample solution. Following procedures were similar to those of ionic halogens. Standard solutions of Cl, Br, and I for the working curves were prepared by the similar procedures.
In order to ascertain the repeatability of samples in different contents of halogens, the amounts of which were determined and the standard deviation was calculated to be 0.150.67. Other metal ions (Na+, K+, Cu2+, Mg2+, Ca2+, Al3+, Bi3+) did not interfere with chlorine determination, even in the coexistence of about 30 times as much in concentration. Moreover, among the anions reactive with silver ions, removal of coexisting sulfur in a sample was studied. For the quantitative analyses of both sulfur-and halogen-containing drugs, silver sulfide was precipitated together with silver chloride in acidic solution. Therefore, in order to remove sulfur as cupric sulfide, excess amounts of cupric nitrate solution (1 mg/ml) was added to the alkaline solution resulted from metallic sodium fusion. Precipitates of cupric sulfide and cupric hydroxide were filtered off, and the filtrate was treated in the same manner as described above.
It has been found that this method, its procedure being very easy and simple, can be made use of even for a small amount of samples (0.251.25 μg Cl/ml, 0.53μg Br/ml, 15 μg I/ml), and so it is applicable to the quantitative determination of halogen-containing drugs.
