Dextromethorphan Hydrobromide

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION 

Dextromethorphan Hydrobromide contains NLT 98.0% and NMT 102.0% of dextromethorphan hydrobromide (C₁₈H₂₅NO . HBr), calculated on the anhydrous basis. 

2 IDENTIFICATION

Change to read: 

2.1 A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020) 

Sample: Dry under vacuum over silica for 4 h. 

Acceptance criteria: Meets the requirements 

2.2 B. 

Buffer: 1.54 g of ammonium acetate in 1 L of water, adjusted with phosphoric acid to a pH of 4.1 

Mobile phase: Methanol and Buffer (90:10) 

Diluent: Methanol and water (90:10) 

System suitability solution: 10 µg/mL of levomethorphan from USP Levomethorphan Solution RS and 10 mg/mL of USP Dextromethorphan Hydrobromide RS in Diluent 

Standard solution: 10 µg/mL of USP Dextromethorphan Hydrobromide RS in Diluent 

Sample solution: 10.0 mg/mL of Dextromethorphan Hydrobromide in Diluent 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: 225 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L88 

Flow rate: 1 mL/min 

Injection volume: 4 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—The relative retention times for dextromethorphan and levomethorphan are 1.0 and 1.28, respectively.] Suitability requirements 

Resolution: NLT 2.0 between dextromethorphan and levomethorphan, System suitability solution 

Relative standard deviation: NMT 5.0% for dextromethorphan, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of levomethorphan in the portion of Dextromethorphan Hydrobromide taken: 

Result = (r_u/r_s) × (C_s/C_u) × (M_r1/M_r2) × 100 

r_u = peak response of levomethorphan from the Sample solution 

r_s = peak response of dextromethorphan from the Standard solution 

C_s = concentration of USP Dextromethorphan Hydrobromide RS in the Standard solution (mg/mL) 

C_u = concentration of Dextromethorphan Hydrobromide in the Sample solution (mg/mL) 

M_r1 = molecular weight of dextromethorphan, 271.40 

M_r2 = molecular weight of dextromethorphan hydrobromide, 352.32

Acceptance criteria: NMT 0.10% 

3 ASSAY 

3.1 Procedure 

Mobile phase: 0.007 M Docusate sodium and 0.007 M ammonium nitrate in acetonitrile and water (70:30), ltered and degassed. Dissolve the docusate sodium in the acetonitrile and water mixture before adding the ammonium nitrate. Adjust the solution with glacial acetic acid to a pH of 3.4. 

Standard stock solution: 1 mg/mL of USP Dextromethorphan Hydrobromide RS in water 

Standard solution: 0.1 mg/mL of USP Dextromethorphan Hydrobromide RS from Standard stock solution in Mobile phase Sample stock solution: 1 mg/mL of Dextromethorphan Hydrobromide in water 

Sample solution: 0.1 mg/mL of Dextromethorphan Hydrobromide from Sample stock solution in Mobile phase 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 280 nm 

Column: 4.6-mm × 25-cm; 5-µm packing L1 

Flow rate: 1 mL/min 

Injection volume: 20 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.5 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of dextromethorphan hydrobromide (C₁₈H₂₅NO . HBr) in the portion of Dextromethorphan Hydrobromide taken: 

Result = (r_u/r_s) × (C_s/C_u) × 100 

r_u = peak response from the Sample solution 

r_s = peak response from the Standard solution 

C_s = concentration of USP Dextromethorphan Hydrobromide RS in the Standard solution (mg/mL) 

C_u = concentration of Dextromethorphan Hydrobromide in the Sample solution (mg/mL) 

Acceptance criteria: 98.0%–102.0% on the anhydrous basis 

4 IMPURITIES 

4.1 Residue on Ignition 〈281〉: NMT 0.1% 

4.2 Limit of Phenolic Compounds 

Sample: 5 mg of Dextromethorphan Hydrobromide 

Analysis: To the Sample add 1 drop of 3 N hydrochloric acid, 1 mL of water, and 2 drops of ferric chloride TS. Add 2 drops of potassium ferricyanide TS, and observe after 2 min. 

Acceptance criteria: No blue-green color develops. 

4.3 Limit of N,N-Dimethylaniline 

Standard solution: Transfer 50 mg of N,N-dimethylaniline to a 100-mL volumetric ask. Add 70.0 mL of water, insert the stopper tightly, shake for 20 min using a mechanical wrist-action shaker or equivalent, and dilute with water to volume. Transfer 1.0 mL to a 100-mL volumetric ask, and dilute with water to volume. Transfer 1.0 mL of the resulting solution to a 25-mL volumetric ask, and add 19 mL of water. Sample solution: Transfer 500 mg of Dextromethorphan Hydrobromide to a 25-mL volumetric ask. Add 19 mL of water and 1 mL of 3 N hydrochloric acid. Dissolve by warming on a steam bath, and cool. 

Analysis: Add 2 mL of 1 N acetic acid and 1 mL of sodium nitrite solution (1 in 100) to the Sample solution, and dilute with water to volume. This solution shows no more color than the straw yellow to greenish yellow color of the Standard solution similarly treated. Acceptance criteria: NMT 0.001% of N,N-dimethylaniline 

5 SPECIFIC TESTS 

5.1 pH 〈791〉 

Sample solution: 10 mg/mL 

Acceptance criteria: 5.2–6.5 

5.2 Water Determination 〈921〉, Method I, Method Ia: 3.5%–5.5% 

6 ADDITIONAL REQUIREMENTS 

6.1 Packaging and Storage: Preserve in tight containers. 

6.2 USP Reference Standards 〈11〉 

USP Dextromethorphan Hydrobromide RS 

USP Levomethorphan Solution RS 

3-Methoxy-17-methylmorphinan. 

C₁₈H₂₅NO          271.40 

This solution contains 0.1 mg/mL of levomethorphan in methanol.