Dimenhydrinate 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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Dimenhydrinate Oral Solution contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of dimenhydrinate (C₁₇H₂₁NO · C₇H₇ClN₄O₂).

1 Packaging and storage

Preserve in tight containers.

2 USP Reference standards 〈11〉

USP Dimenhydrinate RS

3 Identification

The relative retention times of the major peaks for 8-chlorotheophylline and Diphenhydramine in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation, as obtained in the Assay.

Change to read:

4 Content of 8-chlorotheophylline

Ammonium bicarbonate solution-Dissolve 4 g of ammonium bicarbonate in 250 mL of water.

Diluent-Dissolve 4 g of ammonium bicarbonate in 200 mL of water. Add 50 mL of methanol, and mix.

Solution A-Dissolve 0.8 g of ammonium bicarbonate in 800 mL of water. Add 200 mL of methanol, filter, and degas.

Solution B-Dissolve 0.8 g of ammonium bicarbonate in 150 mL of water. Add 850 mL of methanol, filter, and degas.

Mobile phase-Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 〈621〉).

Internal standard solution-Prepare a solution in methanol containing 2.0 mg of 2-hydroxybenzyl alcohol per mL. 

Standard solution-Accurately weigh about 50 mg of USP Dimenhydrinate RS, add about 5 mL of Ammonium bicarbonate solution and 20.0 mL of Internal standard solution, and mix. To 1 mL of this solution add about 9 mL of Diluent, and mix.

Chromatographic system (see Chromatography 〈621〉)-The liquid chromatograph is equipped with a 229-nm detector and a 4.6-mm × 25-cm column that contains packing L7. The flow rate is about 1.5 mL per minute. The chromatograph is programmed as follows.

Chromatograph the Standard solution, and record the peak areas as directed for Procedure: the relative retention times are about 0.3 for 8-chlorotheophylline, 0.5 for the internal standard, and 1.0 for diphenhydramine; the resolution, R, between 8-chlorotheophylline and the internal standard is not less than 4.5; and the relative standard deviation for replicate injections is not more than 2.0%. 

Test solution-Prepare as directed for Assay preparation in the Assay.

Procedure-Separately inject equal volumes (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg per mL, of 8-chlorotheophylline (C₇H₇ClN₄O₂) in the portion of Oral Solution taken by the formula:

(214.61/469.96)(0.05W)(Rᵤ/Rₛ)

in which 214.61 and 469.96 are the molecular weights of 8-chlorotheophylline and dimenhydrinate, respectively; W is the weight, in mg, of USP Dimenhydrinate RS in the Standard solution; and Rᵤ and Rₛ are peak area ratios of 8-chlorotheophylline to the internal standard obtained from the Test solution and the Standard solution, respectively. An amount of 8-chlorotheophylline that is between 43.4% and 47.9% of the amount of dimenhydrinate obtained in the Assay is found.

Alcohol Determination 〈611〉: between 4.0% and 6.0% of C₂H₅OH.

Change to read:

5 Assay

Ammonium bicarbonate solution-Dissolve 4 g of ammonium bicarbonate in 250 mL of water.

Diluent-Dissolve 4 g of ammonium bicarbonate in 200 mL of water. Add 50 mL of methanol, and mix.

Solution A-Dissolve 0.8 g of ammonium bicarbonate in 800 mL of water. Add 200 mL of methanol, filter, and degas.

Solution B-Dissolve 0.8 g of ammonium bicarbonate in 150 mL of water. Add 850 mL of methanol, filter, and degas.

Mobile phase-Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 〈621〉).

Internal standard solution-Prepare a solution in methanol containing 2.0 mg of 2-hydroxybenzyl alcohol per mL.

Standard preparation-Accurately weigh about 50 mg of USP Dimenhydrinate RS, add about 5 mL of Ammonium bicarbonate solution and 20.0 mL of Internal standard solution, and mix. To 1 mL of this solution add about 9 mL of Diluent, and mix.

Chromatographic system (see Chromatography 〈621〉)-The liquid chromatograph is equipped with a 229-nm detector and a 4.6-mm × 25-cm column that contains packing L7. The flow rate is about 1.5 mL per minute. The chromatograph is programmed as follows.

Chromatograph the Standard preparation, and record the peak areas as directed for Procedure: the relative retention times are about 0.3 for 8-chlorotheophylline, 0.5 for the internal standard, and 1.0 for diphenhydramine; the resolution, R, between 8-chlorotheophylline and the internal standard is not less than 4.5; and the relative standard deviation for replicate injections is not more than 2.0%. 

Assay preparation-Pipet 5.0 mL of Oral Solution into a suitable container, add 5.0 mL of Internal standard solution, and mix. Transfer about 1 mL of this solution to a suitable container, add about 5 mL of Diluent, and mix.

Procedure-Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg per mL, of dimenhydrinate (C₁₇H₂₁NO · C₇H₇ClN₄O₂) in the portion of the Oral Solution taken by the formula:

0.05W(Rᵤ/Rₛ)

in which W is the weight, in mg, of USP Dimenhydrinate RS in the Standard preparation; and Rᵤ and Rₛ are the peak area ratios of diphenhydramine to the internal standard obtained from the Assay preparation and the Standard preparation, respectively.