Codeine Sulfate
(C18H21NO3)2·H2SO4·3H2O 750.85

Morphinan-6-ol, 7,8-didehydro-4,5-epoxy-3-methoxy-17-methyl-, (5,6)-, sulfate (2:1) (salt), trihydrate.
7,8-Didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol sulfate (2:1) (salt) trihydrate [6854-40-6].

Anhydrous 696.82 [1420-53-7].
» Codeine Sulfate, dried at 105 for 3 hours, contains not less than 98.5 percent and not more than 100.5 percent of (C18H21NO3)2·H2SO4.
Packaging and storage— Preserve in tight, light-resistant containers.
B: Ultraviolet Absorption 197U
Solution: 100 µg per mL.
Medium: water.
Absorptivities at 284 nm, calculated on the dried basis, do not differ by more than 3.0%.
C: It responds to the tests for Sulfate 191.
Specific rotation 781S: between 112.5 and 115.0.
Test solution: 20 mg per mL, in water.
Acidity— Dissolve 500 mg in 15 mL of water, add 1 drop of methyl red TS, and titrate with 0.020 N sodium hydroxide: not more than 0.30 mL is required for neutralization.
Water, Method III 921 Dry about 500 mg, accurately weighed, at 105 for 3 hours: it loses between 6.0% and 7.5% of its weight.
Readily carbonizable substances 271 Dissolve 10 mg in 5 mL of sulfuric acid TS: the solution has no more color than Matching Fluid S.
Residue on ignition 281: not more than 0.1%.
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 Sulfate (1 in 100): no blue color is produced immediately.
Chromatographic purity— Using Codeine Sulfate, 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 1.4 g of Codeine Sulfate, previously dried and accurately weighed, in 50 mL of glacial acetic acid, warming, if necessary, to effect solution. 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 69.68 mg of (C18H21NO3)2·H2SO4.
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 2016
Pharmacopeial Forum: Volume No. 34(5) Page 1151