Pseudoephedrine Hydrochloride, Carbinoxamine Maleate, and Dextromethorphan Hydrobromide Oral Solution

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

Pseudoephedrine Hydrochloride, Carbinoxamine Maleate, and Dextromethorphan Hydrobromide Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amounts of carbinoxamine maleate (C₁₆H₁₉ClN₂O . C₄H₄O₄), dextromethorphan hydrobromide (C₁₈H₂₅NO . HBr), and pseudoephedrine hydrochloride (C₁₀H₁₅NO . HCl).

2 IDENTIFICATION

A. The retention times of the carbinoxamine maleate and dextromethorphan hydrobromide peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay for Carbinoxamine Maleate and Dextromethorphan Hydrobromide.

B. The retention time of the pseudoephedrine hydrochloride peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay for Pseudoephedrine Hydrochloride.

3 ASSAY

3.1 Carbinoxamine Maleate and Dextromethorphan Hydrobromide

Buffer: Dissolve about 4.4 g of dibasic potassium phosphate in 1000 mL of water. Adjust with phosphoric acid to a pH of 5.5.

Mobile phase: Methanol and Buffer (600:400)

Standard solution: 0.1 mg/mL of carbinoxamine maleate and 0.3 mg/mL of dextromethorphan hydrobromide from USP Carbinoxamine Maleate RS and USP Dextromethorphan Hydrobromide RS in water

Sample solution: Nominally 0.1 mg/mL of carbinoxamine maleate and 0.3 mg/mL of dextromethorphan hydrobromide from a suitable volume of Oral Solution in water

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm × 25-cm; packing L9

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[Note—The relative retention times for dextromethorphan and carbinoxamine are 0.8 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between carbinoxamine and dextromethorphan

Tailing factor: NMT 2.0 for the dextromethorphan peak

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentages of the labeled amounts of carbinoxamine maleate (C₁₆H₁₉ClN₂O . C₄H₄O₄) and of dextromethorphan hydrobromide (C₁₈H₂₅NO . HBr) in the portion of Oral Solution taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of the appropriate analyte from the Sample solution

r_S = peak response of the appropriate analyte from the Standard solution

C_S = concentration of the appropriate Reference Standard in the Standard solution (mg/mL)

C_U = nominal concentration of the appropriate analyte in the Sample solution (mg/mL)

Acceptance criteria:

90.0%–110.0% of the labeled amount of carbinoxamine maleate (C₁₆H₁₉ClN₂O . C₄H₄O₄) and

90.0%–110.0% of the labeled amount of dextromethorphan hydrobromide (C₁₈H₂₅NO . HBr)

3.2 Pseudoephedrine Hydrochloride

Buffer: Dissolve about 4.4 g of dibasic potassium phosphate in 1000 mL of water. Adjust with phosphoric acid to a pH of 5.5.

Mobile phase: Methanol and Buffer (600:400)

Standard solution: 1.2 mg/mL of pseudoephedrine hydrochloride from USP Pseudoephedrine Hydrochloride RS in water

Sample solution: Nominally 1.2 mg/mL of pseudoephedrine hydrochloride from a suitable volume of Oral Solution in water

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 257 nm

Column: 4.6-mm × 25-cm; packing L9

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 1000 theoretical plates

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of pseudoephedrine hydrochloride (C₁₈H₂₅NO . HBr) in the portion of Oral Solution taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of pseudoephedrine from the Sample solution

r_S = peak response of pseudoephedrine from the Standard solution

C_S = concentration of USP Pseudoephedrine Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of pseudoephedrine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0% of the labeled amount of pseudoephedrine hydrochloride (C₁₀H₁₅NO . HCl)

4 PERFORMANCE TESTS

4.1 Uniformity of Dosage Units 〈905〉

For single-unit containers

Acceptance criteria: Meets the requirements

4.2 Deliverable Volume 〈698〉

For multiple-unit containers

Acceptance criteria: Meets the requirements

5 SPECIFIC TESTS

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count does not exceed 10² cfu/g, the total combined molds and yeasts count does not exceed 10¹ cfu/g, and it meets the requirements of the tests for absence of Salmonella species and Escherichia coli.

pH 〈791〉: 3.0–5.0

Alcohol Determination, Method II 〈611〉 (if present): 90.0%–110.0% of the labeled amount of alcohol (C₂H₅OH) is found.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Carbinoxamine Maleate RS

USP Dextromethorphan Hydrobromide RS

USP Pseudoephedrine Hydrochloride RS