Codeine Sulfate Tablets
DEFINITION
Codeine Sulfate Tablets contain NLT 93.0% and NMT 107.0% of the labeled amount of (C18H21NO3)2·H2SO4·3H2O.
IDENTIFICATION
• A. Infrared Absorption 197K
Standard solution:
50 mg of USP Codeine Sulfate RS dissolved in 15 mL of water, then rendered alkaline with 6 N ammonium hydroxide and extracted with several 10-mL portions of chloroform, followed by evaporation of the combined chloroform extracts on a steam bath to dryness, drying at 80 for 4 h
Sample solution:
Digest an equivalent to 50 mg of codeine sulfate, from finely powdered Tablets, with 15 mL of water and 5 mL of 2 N sulfuric acid for 1 h. Filter, if necessary, and wash any undissolved residue with a few mL of water. Render the filtrate alkaline with 6 N ammonium hydroxide, extract with several small portions of chloroform, and evaporate the chloroform solution on a steam bath to dryness, drying at 80 for 4 h.
• B. Identification TestsGeneral, Sulfate 191:
A filtered solution of Tablets meets the requirements.
ASSAY
• Procedure
Diluent:
0.5% of phosphoric acid (5 mL of concentrated phosphoric acid and 1000 mL of water)
Solution A:
Acetonitrile and 0.1% ammonium hydroxide (1.0 mL of concentrated ammonium hydroxide and 1000 mL of water) (1:19)
Solution B:
Acetonitrile and 0.1% ammonium hydroxide (9:11)
Mobile phase:
See the gradient table below.
[NoteThe Standard and Sample solutions, for the degradation products, are stable for 4 days when stored at room temperature in amber vials. ]
Standard solution:
1.2 mg/mL of USP Codeine Sulfate RS in Diluent
Sensitivity solution:
0.6 µg/mL of USP Codeine Sulfate RS from the Standard solution in Diluent
Sample solution:
1.2 mg/mL of codeine sulfate in Diluent. [NoteDissolve 20 Tablets in 80% of the flask volume of Diluent, and sonicate for 1530 min with occasional swirling before diluting with Diluent to volume. ]
Chromatographic system
Mode:
LC
Detector:
UV 282 nm
Column:
4.6-mm × 15-cm; 3-µm packing L1
Column temperature:
40
Flow rate:
1.2 mL/min
Injection size:
40 µL
System suitability
Samples:
Standard solution and Sensitivity solution
Suitability requirements
Relative standard deviation:
NMT 2.0%, Standard solution
Tailing factor:
NMT 2.0, Standard solution
Column efficiency:
NLT 10,000 theoretical plates, Standard solution
Signal-to-noise ratio:
NLT 10, Sensitivity solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of (C18H21NO3)2·H2SO4·3H2O in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
Acceptance criteria:
93.0%107.0%
PERFORMANCE TESTS
• Dissolution 711
Medium:
Water; 500 mL
Apparatus 2:
25 rpm
Time:
45 min
Detector:
UV, maxima at about 284 nm
Cell:
1 cm
Blank:
Medium
Standard solution:
USP Codeine Sulfate RS in Medium
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.8-µm pore size.
Tolerances:
NLT 75% (Q) of the labeled amount of (C18H21NO3)2·H2SO4·3H2O is dissolved.
• Uniformity of Dosage Units 905
Procedure for content uniformity
Standard solution:
110 µg/mL of USP Codeine Sulfate RS in 0.2 N sulfuric acid
Sample solution:
Transfer 1 Tablet to a 50-mL volumetric flask. Add 20 mL of 0.5 N sulfuric acid and 10 mL of water. Shake until the Tablet is disintegrated, and allow to stand for 16 h. Dilute with water to volume, and filter, discarding the first few mL of the filtrate. Dilute the resulting filtrate with 0.2 N sulfuric acid to obtain a solution containing nominally 120 µg/mL of codeine sulfate (trihydrate).
Spectrometric conditions
Mode:
UV-Vis
Analytical wavelength:
About 284 nm
Cell:
1 cm
Blank:
0.2 N sulfuric acid
Analysis
Samples:
Standard solution, Sample solution, and Blank
Calculate the percentage of (C18H21NO3)2·H2SO4·3H2O in the Tablet taken:
Result = (AU/AS) × (CS/CU) × (Mr1/Mr2) × 100
Acceptance criteria:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Diluent, Solution A, Solution B, Mobile phase, Standard solution, Sensitivity solution, Sample solution, Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each individual impurity in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 0.5%
Impurity Table 1
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 2761
Pharmacopeial Forum: Volume No. 36(4) Page 911
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