The following methods are provided for the determination of sulfur dioxide in pharmaceutical excipients.

Mix 20 g of the test specimen, accurately weighed, with 200 mL of an appropriate solvent as indicated in each individual monograph, and stir until a smooth suspension is obtained. Allow the test specimen mixture to remain undisturbed until most of the test specimen has settled, and filter the aqueous portion through paper (Whatman No. 1 or equivalent). To 100 mL of the clear filtrate add an additional solvent as indicated in each individual monograph, add 3 mL of starch TS, and titrate with 0.01 N iodine solution VS to the first permanent blue or purple color. Each 1.0 mL of 0.01 N iodine solution VS consumed corresponds to 0.003% of sulfur dioxide found.

Transfer about 50 to 100 g of the substance to be tested, accurately weighed, to a 250-mL conical flask, add 100 to 150 mL of water, and mix. Cool to between 5 and 10. While stirring with a magnetic stirrer, add 10 mL of cold 1.5 N sodium hydroxide (at a temperature between 5 and 10). Stir for an additional 20 seconds, and add 10 mL of starch indicator solution, prepared as follows: mix 10 g of soluble starch with 50 mL of cold water, transfer to 1000 mL of boiling water, stir until completely dissolved, cool, and add 1 g of salicylic acid preservative. [note—Discard the solution after 1 month.] Add 10 mL of 2.0 N sulfuric acid (at a temperature between 5 and 10), and titrate immediately with 0.005 N iodine VS until a light blue color persists for 1 minute (see Titrimetry 541). Perform a blank determination, using 200 mL of water treated similarly to the solution under test, and make any necessary correction. Each mL of 0.005 N iodine is equivalent to 0.16 mg of SO2.

Dissolve 20.0 g of the test specimen in 150 mL of hot water in a flask having a round bottom and a long neck, add 5 mL of phosphoric acid and 1 g of sodium bicarbonate, and at once connect the flask to a condenser. [note—Excessive foaming can be alleviated by the addition of a few drops of a suitable antifoaming agent.] Distill 50 mL, receiving the distillate under the surface of 50 mL of 0.1 N iodine. Acidify the distillate with a few drops of hydrochloric acid, add 2 mL of barium chloride TS, and heat on a steam bath until the liquid is nearly colorless. The precipitate of barium sulfate, if any, when filtered, washed, and ignited, weighs not more than 3 mg, corresponding to not more than 0.004% of sulfur dioxide, correction being made for any sulfate that may be present in 50 mL of the 0.1 N iodine.

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