Dextromethorphan

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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C₁₈H₂₅NO    271.40

Morphinan, 3-methoxy-17-methyl-, (9α,13α,14α)-;

3-Methoxy-17-methyl-9α,13α,14α-morphinan   CAS RN®: 125-71-3; UNII: 7355X3ROTS.

1 DEFINITION

Dextromethorphan contains NLT 98.0% and NMT 101.0% of dextromethorphan (C₁₈H₂₅NO), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

2.1 A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

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 RS in Diluent

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

Sample solution: 10.0 mg/mL of Dextromethorphan 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 taken:

Result = (r_u/r_s) × (C_s/C_u) × 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 RS in the Standard solution (mg/mL)

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

Acceptance criteria: NMT 0.10%

3 ASSAY

3.1 Procedure

Sample solution: Dissolve 700 mg of Dextromethorphan in 60 mL of glacial acetic acid, warming slightly, if necessary, to dissolve.

Titrimetric system

Mode: Direct titration

Titrant: 0.1 N perchloric acid VS

Endpoint detection: Visual

Analysis: Add 2 drops of crystal violet TS to the Sample solution and titrate with Titrant to a blue-green endpoint. Perform a blank determination and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 27.14 mg of dextromethorphan (C₁₈H₂₅NO).

Acceptance criteria: 98.0%–101.0% on the anhydrous basis

4 IMPURITIES

4.1 Residue on Ignition 〈281〉: NMT 0.1%

4.2 Limit of Phenolic Compounds

Sample: 10 mg of Dextromethorphan

Analysis: Dissolve the Sample in 2 mL of 3 N hydrochloric acid, add 2 drops of ferric chloride TS, and mix. 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 flask, add 70.0 mL of water, insert 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 flask and dilute to volume. Transfer 1.0 mL of this solution to a 25-mL volumetric flask and add 19 mL of water.

Sample solution: Transfer 500 mg of Dextromethorphan to a 25-mL volumetric flask, 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

Water Determination 〈921〉, Method I, Method Ia: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Dextromethorphan RS

USP Levomethorphan Solution RS

3-Methoxy-17-methylmorphinan.

C₁₈H₂₅NO 271.40

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