Dimenhydrinate Injection

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 Injection is a solution of Dimenhydrinate in a mixture of Propylene Glycol and water. It contains not less than 95.0 percent and not more than 105.0 percent of the labeled amount of dimenhydrinate (C₁₇H₂₁NO · C₇H₇ClN₄O₂).

1 Packaging and storage

Preserve in single-dose or multiple-dose containers, preferably of Type I or Type III glass.

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.

pH 〈791〉: between 6.4 and 7.2.

4 Content of 8-chlorotheophylline

Mobile phase-Dissolve 0.81 g of dl-10-camphorsulfonic acid and 0.70 g of sodium acetate in 700 mL of water. Add 300 mL of methanol, mix, and pass through a membrane filter having a 0.5-µm or finer porosity.

Standard solution-Dissolve an accurately weighed quantity of USP Dimenhydrinate RS in methanol to obtain a Standard stock solution having a known concentration of about 0.5 mg per mL. Retain a portion of this Standard stock solution for use in the Assay. Pipet 5 mL into a 50-mL volumetric flask, dilute with methanol to volume, mix, and pass through a membrane filter having a 0.5-µm or finer porosity.

Test solution-Transfer an accurately measured volume of Injection, equivalent to about 50 mg of dimenhydrinate, to a 100-mL volumetric flask, dilute with methanol to volume, and mix to obtain a stock solution. Retain a portion of this stock solution for use in the Assay. Pipet 5 mL of this stock solution into a 50-mL volumetric flask, dilute with methanol to volume, mix, and pass through a membrane filter having a 0.5-µm or finer porosity.

Chromatographic system (see Chromatography 〈621〉)-The liquid chromatograph is equipped with a 280-nm detector, a 2-mm × 12.5-cm guard column that contains packing L2, and a 4.6-mm × 25-cm analytical column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph three replicate injections of the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation is not more than 1.0%.

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 responses for the major peaks. Calculate the quantity, in mg, of 8-chlorotheophylline (C₇H₇ClN₄O₂) in each mL of the Injection taken by the formula:

(214.61/469.96)(1000C/V)(rᵤ/rₛ)

in which 214.61 and 469.96 are the molecular weights of 8-chlorotheophylline and dimenhydrinate, respectively; C is the concentration, in mg per mL, of USP Dimenhydrinate RS in the Standard solution; V is the volume, in mL, of Injection taken; and rᵤ and rₛ are the peak responses 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.

5 Other requirements

It meets the requirements under Injections and Implanted Drug Products 〈1〉.

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6 Assay

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-Use a portion of the Standard stock solution that was prepared for the Standard solution in the test for Content of 8-chlorotheophylline. Mix 5.0 mL of this Standard stock solution and 5.0 mL of Internal standard solution, and pass through a membrane filter having a 0.5-µm or finer porosity.

Assay preparation-Use a portion of the stock solution that was prepared for the Test solution in the test for Content of 8-chlorotheophylline. Mix 5.0 mL of this stock solution and 5.0 mL of Internal standard solution, and pass through a membrane filter having a 0.5-µm or finer porosity.

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%.

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, of dimenhydrinate (C₁₇H₂₁NO · C₇H₇ClN₄O₂) in each mL of the Injection taken by the formula:

(200C/V)(Rᵤ/Rₛ)

in which C is the concentration of USP Dimenhydrinate RS in the Standard preparation; V is the volume, in mL, of Injection taken; 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.