Identification—
A:
Evaporate to about one-half its volume on a steam bath a portion, equivalent to about 500 mg of aminophylline, of the water solution prepared in the
Assay. Adjust with 1 N sodium hydroxide to a pH of 7.0, chill, and filter the crystals of theophylline. Save the filtrate, free from the washings, for use in
Identification test
B: the crystals, after being washed with small portions of ice-cold water and dried at 105
for 1 hour, melt between 270
and 274
, and respond to
Identification test
B under
Aminophylline.
Ethylenediamine content—
Accurately weigh a portion of the stirred, congealed mass of the Suppositories used for the
Assay, equivalent to about 500 mg of aminophylline, and place in a 500-mL conical flask. Add 150 mL of a mixture of equal volumes of alcohol and ether, and warm gently under reflux for 30 minutes, with occasional swirling. Cool to room temperature, and titrate with 0.1 N hydrochloric acid VS, using a glass-modified calomel electrode system (replace the saturated potassium chloride solution of the calomel electrode with methanol saturated with lithium chloride). Each mL of 0.1 N hydrochloric acid is equivalent to 3.005 mg of C
2H
8N
2. The Suppositories contain between 152 mg and 190 mg of ethylenediamine (C
2H
8N
2) per g of C
7H
8N
4O
2 found in the
Assay.
Assay—
Tare a small dish and a glass rod, place in the dish not less than 5 Suppositories, and heat on a steam bath until melted. Mix the melt by stirring it with the rod, cool while stirring, and weigh. Weigh accurately a portion of the mass, equivalent to about 1 g of aminophylline, place it in a beaker, add 60 mL of hot water and 3 mL of nitric acid, and heat on a steam bath for 15 minutes with frequent stirring. Cool, transfer to a separator with the aid of 40 mL of ether, shake well, and allow to separate, using a few mL of alcohol, if necessary, to bring about separation of any emulsion that has formed. Draw the water layer into a 100-mL volumetric flask, wash the ether with two 15-mL portions of water, adding the washings to the volumetric flask, dilute with water to volume, and mix. Transfer an accurately measured portion of the solution, equivalent to about 250 mg of aminophylline, to a 250-mL conical flask, add 10 mL of 6 N ammonium hydroxide and about 20 mL of 0.1 N silver nitrate VS, and heat on a steam bath for 15 minutes. Cool to between 5
and 10
for 20 minutes, then filter, preferably through a filtering crucible of fine porosity under reduced pressure, and wash the precipitate with small portions of water until the last washing gives not more than a faint opalescence with hydrochloric acid. Dissolve the precipitate by pouring over it small volumes of warm 2 N nitric acid, receiving the solution in a conical flask. Wash the filtering crucible a few times with warm water acidified with nitric acid, receiving the washings in the same flask. Cool, add 2 mL of
ferric ammonium sulfate TS, and titrate with 0.1 N ammonium thiocyanate VS. Each mL of 0.1 N ammonium thiocyanate is equivalent to 18.02 mg of theophylline (C
7H
8N
4O
2).
467
:
meet the requirements.