(dye hye'' droe koe' deen bye tar' trate).
Morphinan-6-ol, 4,5-epoxy-3-methoxy-17-methyl-, (5,6)-2,3-dihydroxybutanedioate (1:1) (salt).
4,5-Epoxy-3-methoxy-17-methylmorphinan-6-ol (+)-tartrate (salt).
» Dihydrocodeine Bitartrate contains not less than 98.0 percent and not more than 102.0 percent of C18H23NO3·C4H6O6, calculated on the dried basis.
Packaging and storage Preserve in tight containers.
USP Reference standards 11
A: The chromatogram of the Assay preparation obtained as directed in the Assay exhibits a major peak for dihydrocodeine, the retention time of which corresponds to that in the chromatogram of the Standard preparation similarly determined.
B: It responds to the tests for Tartrate 191.
C: To a solution of 20 mg in 5 mL of sulfuric acid in a test tube add 1 drop of ferric chloride TS, and heat in a boiling water bath for 2 minutes: although the solution may darken, no blue color is produced (distinction from codeine and morphine).
Melting range, Class I 741: between 186 and 190, but the range between beginning and end of melting does not exceed 2.5.
Specific rotation 781S: between 72 and 75.
Test solution: 10 mg per mL, in water.
pH 791: between 3.2 and 4.2, in a solution (1 in 10).
Loss on drying 731 Dry it at 105 for 4 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%.
Ammonium salts To about 100 mg of it in a suitable test tube add 5 mL of 1 N sodium hydroxide, and heat on a steam bath: the odor of ammonia is not detected.
Ordinary impurities 466
Test solution: water.
Standard solution: water.
Eluant: a mixture of methylene chloride, methanol, and ammonium hydroxide (90:10:1).
Visualization: 17, and view under short-wavelength UV light.
Mobile phase Prepare a mixture of acetonitrile, water, and diethylamine (800:4:1). Prepare a suitable mixture of this solution and methanol (55:45). Make adjustments if necessary (see System Suitability under Chromatography 621).
Resolution solution Prepare a solution in methanol containing about 0.4 mg of USP Dihydrocodeine Bitartrate RS and 0.6 mg of hydrocodone bitartrate per mL. Prepare a mixture of this solution and water (1:1).
Standard preparation Transfer about 20 mg of USP Dihydrocodeine Bitartrate RS, accurately weighed, to a 50-mL volumetric flask, add 25 mL of methanol, swirl to dissolve, dilute with water to volume, and mix.
Assay preparation Transfer about 20 mg of Dihydrocodeine Bitartrate, accurately weighed, to a 50-mL volumetric flask, add 25 mL of methanol, swirl to dissolve, dilute with water to volume, and mix.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 280-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L3. The flow rate is about 1.5 mL per minute. Chromatograph the Resolution solution, and record the responses as directed under Procedure: the relative retention times are about 0.8 for hydrocodone and 1.0 for dihydrocodeine, and the resolution, R, between the hydrocodone and dihydrocodeine peaks is not less than 1.8. Chromatograph the Standard preparation, and record the responses as directed under Procedure: the column efficiency determined from the dihydrocodeine peak is not less than 900 theoretical plates, the tailing factor for the dihydrocodeine peak is not more than 1.7, and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 25 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C18H23NO3·C4H6O6 in the portion of Dihydrocodeine Bitartrate taken by the formula:
50C(rU / rS)in which C is the concentration, in mg per mL, of USP Dihydrocodeine Bitartrate RS in the Standard preparation, and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 2907Pharmacopeial Forum: Volume No. 33(3) Page 396