Codeine
;)
Morphinan-6-ol,7,8-didehydro-4,5-epoxy-3-methoxy-17-methyl-,monohydrate,(5a,6a)-.
7,8-Didehydro-4,5a-epoxy-3-methoxy-17-methylmorphinan-6a-ol monohydrate [6059-47-8].
Anhydrous 299.37 [76-57-3].
»Codeine,dried at 80
for 4hours,contains not less than 98.5percent and not more than 100.5percent of C18H21NO3.
for 4hours,contains not less than 98.5percent and not more than 100.5percent of C18H21NO3.
Packaging and storage—
Preserve in tight,light-resistant containers.
Identification—
A:
Infrared Absorption á197Kñ—Proceed as directed with the codeine test specimen and the codeine standard specimen obtained from 50mg of USP Codeine Sulfate RSdissolved in 15mLof water,then rendered alkaline with 6Nammonium hydroxide and extracted with several 10-mLportions of chloroform,followed by evaporation of the combined chloroform extracts on a steam bath to dryness,and drying at 80for 4hours.
for 4hours.
B:
Ultraviolet Absorption á197Uñ—
Solution:
100µg per mL.
Medium:
0.1Nsulfuric acid.
Absorptivity at 284nm,calculated on the dried basis,is between 112.9%and 119.9%of that of USP Codeine Sulfate RS.
Melting range á741ñ—
When previously dried,it melts between 154and 158,but the range between beginning and end of melting does not exceed 2.
and 158,but the range between beginning and end of melting does not exceed 2.
Loss on drying á731ñ—
Dry it at 80for 4hours:it loses not more than 6.0%of its weight.
for 4hours:it loses not more than 6.0%of its weight.
Residue on ignition á281ñ:
not more than 0.1%.
Readily carbonizable substances á271ñ—
Dissolve 10mg in 5mLof sulfuric acid TS:the solution has no more color than Matching Fluid S.
Chromatographic purity—
Prepare a solution of it in dehydrated alcohol containing 40mg per mL(Solution A).Dilute 2.0mLof Solution Awith dehydrated alcohol to 100mL(Solution B).Dilute 1.0mLof Solution Awith dehydrated alcohol to 100mL(Solution C).Apply separate 10-µLvolumes of Solution A,Solution B,and Solution Cto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel.Allow the spots to dry,and develop the chromatogram in a solvent system consisting of a mixture of dehydrated alcohol,cyclohexane,and ammonium hydroxide (72:30:6)until the solvent front has moved three-fourths of the length of the plate.Remove the plate from the developing chamber,and allow the solvent to evaporate.Spray the plate with a reagent prepared by mixing 3mLof chloroplatinic acid solution (1in 10)with 97mLof water,followed by the addition of 100mLof potassium iodide solution (6in 100),and examine the chromatogram:no spot obtained from Solution A,other than the principal spot and any spot observed at the origin,is more intense than the principal spot obtained from Solution B(2%);and not more than one such spot having an RFgreater than that of the principal spot is more intense than the principal spot obtained from Solution C(1%).
Limit of morphine—
Dissolve about 50mg of potassium ferricyanide in 10mLof water,and add 1drop of ferric chloride TSand 1mLof a neutral or slightly acid solution of Codeine (1in 100)prepared with the aid of sulfuric acid:no blue color is produced immediately.
Assay—
Dissolve about 400mg of Codeine,previously dried and accurately weighed,by warming it in 30.0mLof 0.1Nsulfuric acid VS.Cool,and add 10mLof water.Add methyl red TS,and titrate the excess acid with 0.1Nsodium hydroxide VS.Perform a blank determination (see Residual Titrationsunder Titrimetry á541ñ).Each mLof 0.1Nsulfuric acid is equivalent to 29.94mg of C18H21NO3.
Auxiliary Information—
Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA2)Pharmaceutical Analysis 2
USP28–NF23Page 535
Phone Number:1-301-816-8139