Diphenhydramine Hydrochloride 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

Diphenhydramine Hydrochloride Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of diphenhydramine hydrochloride (C₁₇H₂₁NO · HCI).

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

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

Change to read:

3.1 PROCEDURE

Solution A: 11.24 g/L of sodium perchlorate monohydrate in water. Add 1 mL of trifluoroacetic acid to each L of solution prepared.

Solution B: Acetonitrile and trifluoroacetic acid (1000:1)

Solution C: Solution A and Solution B (82:18)

Solution D: Solution A and Solution B (50:50)

Mobile phase:

See Table 1.

Table 1 

Diluent: Acetonitrile and water (18:82)

Standard stock solution: 1.0 mg/mL of USP Diphenhydramine Hydrochloride RS in Diluent

Standard solution: 0.25 mg/mL of USP Diphenhydramine Hydrochloride RS from the Standard stock solution

System suitability stock solution: 0.0125 mg/mL of USP Diphenhydramine Related Compound A RS prepared as follows. Transfer an appropriate amount of the Reference Standard to a volumetric flask. Add 5% of the flask volume of acetonitrile and dilute with Diluent to volume. Dilute this solution (1 in 10) with Diluent.

System suitability solution: 0.25 mg/mL of USP Diphenhydramine Hydrochloride RS and 0.00025 mg/mL of USP Diphenhydramine Related Compound A RS in Diluent from the Standard stock solution and System suitability stock solution, respectively

Sample solution: Nominally 0.25 mg/mL of diphenhydramine hydrochloride from a suitable volume of Oral Solution in Diluent. Pass a portion of the resulting solution through a suitable filter of 0.45-um pore size, discarding the first few mL of filtrate. Use the filtrate.

3.1.1 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm. For Identification A, use a diode-array detector in the range of 200-400 nm.

Column: 4.6-mm x 15-cm; 5-µm packing 11

Column temperature: 35°

Flow rate: 1.2 mL/min

Injection volume: 10 µL

3.1.2 System suitability

Samples: Standard solution and System suitability solution

[NOTE-^▲The relative retention times for diphenhydramine related compound A and diphenhydramine are 0.96 and 1.0, respectively. _{▲(RB 1-Nov-2021)}]

3.1.3 Suitability requirements

Resolution: NLT 1.5 between diphenhydramine and diphenhydramine related compound A, System suitability solution

Tailing factor: 0.5-2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

3.1.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of diphenhydramine hydrochloride (C₁₇H₂₁NO · HCI) in the portion of Oral Solution taken:

                Result = (r_U/r_S) x (C_S/C_U) × 100 

r_U = peak response of diphenhydramine from the Sample solution

r_S = peak response of diphenhydramine from the Standard solution

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

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

Acceptance criteria: 90.0%-110.0%

4 OTHER COMPONENTS

ALCOHOL DETERMINATION (611) (if present): 90.0%-110.0% of the labeled amount of Ethanol (C₂H₂OH)

Delete the following:

(RB 1-Nov-2021)

5 PERFORMANCE TESTS

DELIVERABLE VOLUME (698): Meets the requirements

6 SPECIFIC TESTS

PH (791): 3.5-5.5

MICROBIAL ENUMERATION TESTS (61) and TESTS FOR SPECIFIED MICROORGANISMS (62): It meets the requirements of the test for the absence of Escherichia coli. The total aerobic microbial count does not exceed 10² cfu/mL. The total yeasts and molds count does not exceed 10¹ cfu/mL..

7 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Store at controlled room temperature.

Change to read:

USP REFERENCE STANDARDS (11)

(RB 1-Nov-2021)

USP Diphenhydramine Hydrochloride RS

(RB 1-Nov-2021)

USP Diphenhydramine Related Compound A RS

2-(Diphenylmethoxy)-N-methylethanamine hydrochloride.

C₁₆H₁₉NO · HCI             277.79

(RB 1-Nov-2021)