Diphenhydramine Hydrochloride Capsules

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

Diphenhydramine Hydrochloride Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of diphenhydramine hydrochloride (C₁₇H₂₁NO·HCl).

2 IDENTIFICATION

A. Identification-Organic Nitrogenous Bases 〈181〉: The contents of the Capsules meet the requirements.

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Buffer: 5.4 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.0.

Solution A: Buffer

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and Buffer (35:65)

System suitability solution: 0.1 mg/mL each of USP Diphenhydramine Related Compound A RS and USP Diphenhydramine Hydrochloride RS in Diluent

Standard solution: Nominally 0.07 mg/mL of USP Diphenhydramine Hydrochloride RS in Diluent

Sample stock solution: Weigh and combine the contents of NLT 20 Capsules. Transfer an accurately weighed portion of the combined Capsule contents, equivalent to about 50 mg of diphenhydramine hydrochloride, to a 100-mL volumetric flask. Dissolve in and dilute with water to volume, and filter. Alternatively, dissolve NLT 20 Capsules in water at 50° and pipet the solution equivalent to about 50 mg of diphenhydramine hydrochloride to a 100-mL volumetric flask. Dissolve in and dilute with water to volume, and filter.

Sample solution: 0.07 mg/mL of diphenhydramine hydrochloride in Diluent from the Sample stock solution

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 220 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L7
• Flow rate: 1.2 mL/min
• Injection volume: 10 µL

System suitability

• Samples: System suitability solution and Standard solution
• [Note-The relative retention times for diphenhydramine related compound A and diphenhydramine are about 0.9 and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 2.0 between diphenhydramine and diphenhydramine related compound A, System suitability solution
• Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of diphenhydramine hydrochloride (C₁₇H₂₁NO·HCl) in the portion of Capsule contents taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of diphenhydramine from the Sample solution

rₛ = peak response of diphenhydramine from the Standard solution

Cₛ = concentration of USP Diphenhydramine Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of diphenhydramine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

4.1.1 Procedure for a pooled sample

Medium: Water; 500 mL

Apparatus 1: 100 rpm

Time: 30 min

Mobile phase and Chromatographic system: Proceed as directed in the Assay.

Injection volume: 50 µL

Standard solution: USP Diphenhydramine Hydrochloride RS in Medium, at a known concentration similar to that of the Sample solution

Sample solution: Dilute with Medium to a concentration that is similar to that of the Standard solution.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of diphenhydramine hydrochloride (C₁₇H₂₁NO·HCl) dissolved.

Tolerances: NLT 80% (Q) of the labeled amount of diphenhydramine hydrochloride (C₁₇H₂₁NO·HCl) is dissolved.

4.2 Uniformity of Dosage Units 〈905〉: Meet the requirements

Delete the following:

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Diphenhydramine Hydrochloride RS

USP Diphenhydramine Related Compound A RS

2-(Diphenylmethoxy)-N-methylethanamine hydrochloride.

C₁₆H₁₉NO·HCl     277.79