Dimenhydrinate Tablets

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

Dimenhydrinate Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of dimenhydrinate (C₁₇H₂₁NO · C₇H₇ClN₄O₂).

2 IDENTIFICATION

A. The relative retention times for the 8-chlorotheophylline and diphenhydramine peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

B. The UV spectra of the 8-chlorotheophylline and diphenhydramine peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Solution A: 10.0 g/L (equivalent to 13.8 mL/L) of triethylamine in water; adjusted with phosphoric acid to a pH of 2.5

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Return to original conditions, and re-equilibrate the system for NLT 10 min.

Diluent: Acetonitrile and water (18:82)

System suitability solution: 0.114 mg/mL of USP Diphenhydramine Hydrochloride RS and 0.1 mg/mL of USP Diphenhydramine Related Compound A RS in Diluent. Sonicate to dissolve, if necessary.

Standard solution: 0.1 mg/mL of USP Dimenhydrinate RS in Diluent. Sonicate to dissolve, if necessary.

Sample solution: Nominally 0.1 mg/mL of dimenhydrinate in Diluent prepared as follows. Transfer an amount equivalent to 10 mg of dimenhydrinate from finely powdered Tablets (NLT 5) to a 100-mL volumetric flask, and add about 80% of the final volume of Diluent. Sonicate for 5 min, and dilute with Diluent to volume. Centrifuge a portion of the resulting solution and use the supernatant. [Note-A centrifuge speed of 10,000 rpm for 10 min may be suitable.]

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 225 nm. For Identification B, use a diode array detector in the range of 200–400 nm.
• Column: 4.6-mm × 25-cm; 5-µm packing L1
• Column temperature: 30°
• Flow rate: See Table 1.
• Injection volume: 10 µL

System suitability

• Samples: System suitability solution and Standard solution
• [Note-See Table 2 for relative retention times.]
• Suitability requirements
• Resolution: NLT 1.5 between diphenhydramine related compound A and diphenhydramine, System suitability solution
• Tailing factor: NMT 2.0 for 8-chlorotheophylline and diphenhydramine, Standard solution
• Relative standard deviation: NMT 2.0% for 8-chlorotheophylline and diphenhydramine, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of dimenhydrinate (C₁₇H₂₁NO · C₇H₇ClN₄O₂) in the portion of Tablets 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 Dimenhydrinate RS in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

4 OTHER COMPONENTS

Change to read:

4.1 8-Chlorotheophylline

Solution A, Solution B, Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.05 mg/mL of USP 8-Chlorotheophylline RS in Diluent

System suitability

• Sample: Standard solution
• Suitability requirements
• Tailing factor: NMT 2.0
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of 8-chlorotheophylline (C₇H₇ClN₄O₂) in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of 8-chlorotheophylline from the Sample solution

rₛ = peak response of 8-chlorotheophylline from the Standard solution

Cₛ = concentration of USP 8-Chlorotheophylline RS in the Standard solution (mg/mL)

Cᵤ = determined concentration of dimenhydrinate in the Sample solution, as obtained in the Assay (mg/mL)

Acceptance criteria: 43.4%–47.9%

5 PERFORMANCE TESTS

5.1 Dissolution 〈711〉

• Medium: Water; 900 mL
• Apparatus 2: 50 rpm
• Time: 45 min
• Standard solution: USP Dimenhydrinate RS in Medium
• Sample solution: Pass a portion of the solution under test through a suitable filter. Dilute with Medium to a concentration that is similar to the Standard solution, if necessary.
• Instrumental conditions
• Mode: UV
• Analytical wavelength: 276 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of dimenhydrinate (C₁₇H₂₁NO · C₇H₇ClN₄O₂) dissolved:

Result = (Aᵤ/Aₛ) × Cₛ × V × D × 1/L × 100

Aᵤ = absorbance of the Sample solution

Aₛ = absorbance of the Standard solution

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

V = volume of Medium, 900 mL

D = dilution factor of the Sample solution, if applicable

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of dimenhydrinate C₁₇H₂₁NO · C₇H₇ClN₄O₂ is dissolved. 

5.2 Uniformity of Dosage Units 〈905〉: Meet the requirements.

6 IMPURITIES

6.1 Organic Impurities

Solution A, Solution B, Mobile phase, Diluent, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 2.28 µg/mL of USP Diphenhydramine Hydrochloride RS in Diluent

Sensitivity solution: 1.14 µg/mL of USP Diphenhydramine Hydrochloride RS in Diluent, from the Standard solution

Sample solution: Nominally 1.0 mg/mL of dimenhydrinate in Diluent prepared as follows. Transfer an amount equivalent to 20 mg of dimenhydrinate from finely powdered Tablets (NLT 5) to a 20-mL volumetric flask, and add about 40% of the final volume of Diluent. Sonicate for 5 min, and dilute with Diluent to volume. Centrifuge a portion of the resulting solution and use the supernatant. [Note-A centrifuge speed of 10,000 rpm for 10 min may be suitable.]

System suitability

• Samples: System suitability solution, Standard solution, and Sensitivity solution
• Suitability requirements
• Resolution: NLT 1.5 between diphenhydramine related compound A and diphenhydramine, System suitability solution
• Relative standard deviation: NMT 5.0%, Standard solution
• Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × (M_r1/M_r2) × 100

rᵤ = peak response of each individual impurity 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 dimenhydrinate in the Sample solution (mg/mL)

M_r1 = molecular weight of diphenhydramine, 255.36

M_r2 = molecular weight of diphenhydramine hydrochloride, 291.82

Acceptance criteria: See Table 2.

Table 2

ᵃ 1,3-Dimethyl-3,7-dihydro-1H-purine-2,6-dione.

7 ADDITIONAL REQUIREMENTS

7.1 Packaging and Storage

Preserve in well-closed containers. Store at controlled room temperature. Protect from moisture.

7.2 USP Reference Standards 〈11〉

• USP 8-Chlorotheophylline RS
• USP Dimenhydrinate RS
• USP Diphenhydramine Hydrochloride RS
• USP Diphenhydramine Related Compound A RS

2-(Diphenylmethoxy)-N-methylethanamine hydrochloride.

C₁₆H₁₉NO·HCl      277.79