Codeine Phosphate
C18H21NO3·H3PO4·½H2O 406.37

Morphinan-6-ol, 7,8-didehydro-4,5-epoxy-3-methoxy-17-methyl-, (5,6)-, phosphate (1:1) (salt), hemihydrate.
7,8-Didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol phosphate (1:1) (salt) hemihydrate [41444-62-6].

Anhydrous 397.37 [52-28-8].
» Codeine Phosphate contains not less than 99.0 percent and not more than 101.5 percent of C18H21NO3·H3PO4, calculated on the anhydrous basis.
Packaging and storage— Preserve in tight, light-resistant containers. Store up to 40 as permitted by the manufacturer.
B: Neutralize a solution (1 in 50) with 6 N ammonium hydroxide, and add silver nitrate TS: a yellow precipitate of silver phosphate is formed, and it is soluble in 2 N nitric acid and in 6 N ammonium hydroxide.
Acidity— Dissolve 100 mg in 20 mL of water, and titrate with 0.010 N sodium hydroxide to a pH of 5.4, using a pH meter: not more than 1.0 mL of 0.010 N sodium hydroxide is required.
Water, Method I 921: not more than 3.0%.
Chloride— To 10 mL of a solution (1 in 100), acidified with nitric acid, add a few drops of silver nitrate TS: no opalescence is produced immediately.
Sulfate— To 10 mL of a solution (1 in 100) add a few drops of barium chloride TS: no turbidity is produced immediately.
Limit of morphine— Dissolve about 50 mg of potassium ferricyanide in 10 mL of water, and add 1 drop of ferric chloride TS and 1 mL of a solution of Codeine Phosphate (1 in 100): no blue color is produced immediately.
Chromatographic purity— Using Codeine Phosphate, proceed as directed in the test for Chromatographic purity under Codeine, except to use a mixture of 0.01 N hydrochloric acid and dehydrated alcohol (4:1), instead of dehydrated alcohol, to prepare Solution A, Solution B, and Solution C.
Assay— Dissolve about 1 g of Codeine Phosphate, accurately weighed, in 50 mL of glacial acetic acid, warming slightly if necessary to effect solution, and titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 39.74 mg of C18H21NO3·H3PO4.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Clydewyn M. Anthony, Ph.D.
(MDCCA05) Monograph Development-Cough Cold and Analgesics
Reference Standards Lili Wang, Technical Services Scientist
USP32–NF27 Page 2015
Pharmacopeial Forum: Volume No. 30(5) Page 1597