Amantadine 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)

DOWNLOAD PDF HERE

1 DEFINITION

Amantadine Hydrochloride Oral Solution contains NLT 95.0% and NMT 105.0% of the labeled amount of amantadine hydrochloride (C₁₀H₁₇N·HCl).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A, 197K, or 197S (CN 1-May-2020)

Cell: 1 mm

Sample solution: Place a volume of Oral Solution, equivalent to 200 mg of amantadine hydrochloride, in a vessel, dissolve in 0.1 N hydrochloric acid, and filter. Transfer the filtrate to a separator, add 10 mL of 0.5 N sodium hydroxide, and extract with 5 mL of methylene chloride. Filter the extract through anhydrous sodium sulfate, and rinse the anhydrous sodium sulfate with 2 mL of methylene chloride.

Acceptance criteria: Meets 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

Internal standard solution: 0.3 mg/mL of adamantane in n-heptane

Standard stock solution: 1 mg/mL of USP Amantadine Hydrochloride RS in water

Standard solution: Transfer 10 mL of Standard stock solution to a separatory funnel and add 10 mL of 5 N sodium hydroxide solution. Add 25mL of Internal standard solution and shake for 10 min. Collect the n-heptane upper layer and swirl with anhydrous sodium sulfate to remove traces of water.

Sample stock solution: Nominally 1 mg/mL of amantadine hydrochloride from a portion of Oral Solution in water

Sample solution: Transfer 10 mL of Sample stock solution to a separatory funnel and add 10 mL of 5 N sodium hydroxide solution. Add 25 mL of Internal standard solution and shake for 10 min. Collect the n-heptane upper layer and swirl with anhydrous sodium sulfate to remove traces of water.

3.2 Chromatographic system

Mode: GC

Detector: Flame ionization

Column: 0.53-mm × 30-m base deactivated fused-silica; coated with 1.0-μm film of stationary phase G27

Temperatures

Injection port: 220°

Detector: 300°

Column: See Table 1.

Table 1

Carrier gas: Helium

Flow rate: 4 mL/min

Injection volume: 2 μL

Injection type: Split ratio, 5:1 (deactivated split liner with glass wool)

3.3 System suitability

Sample: Standard solution

[Note-The relative retention times for adamantane and amantadine are about 0.7 and 1.0, respectively.]

3.4 Suitability requirements

Tailing factor: NMT 2.0 for the amantadine peak

Relative standard deviation: NMT 2.0% for the peak response ratio of amantadine to adamantane

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of amantadine hydrochloride (C₁₀H₁₇N·HCl) in the portion of Oral Solution taken:

Result = (R_u/R_s) × (C_s/C_u) × 100

R_u = peak response ratio of amantadine to adamantane from the Sample solution

R_s = peak response ratio of amantadine to adamantane from the Standard solution

C_s = concentration of USP Amantadine Hydrochloride RS in the Standard stock solution (mg/mL)

C_u = nominal concentration of amantadine hydrochloride in the Sample stock solution (mg/mL)

Acceptance criteria: 95.0%–105.0%

4 IMPURITIES

4.1 Organic Impurities

Internal standard solution: 0.1 mg/mL of adamantane in n-heptane

Peak identification solution: 0.03 mg/mL each of USP Amantadine Related Compound A RS and USP Amantadine Related Compound B RS in Internal standard solution prepared as follows. Transfer suitable amounts of USP Amantadine Related Compound A RS and USP

Amantadine Related Compound B RS to a suitable volumetric flask. Add methylene chloride to about 5% of the flask volume to dissolve, and dilute with Internal standard solution to volume.

Standard stock solution: 0.03 mg/mL of USP Amantadine Hydrochloride RS in water

Standard solution: Transfer 25 mL of Standard stock solution, 10 mL of 5 N sodium hydroxide solution, and 25 mL of Internal standard solution to a separatory funnel and shake for 10 min. Collect the upper layer of n-heptane and swirl with anhydrous sodium sulfate to remove traces of water.

Sample stock solution: Nominally 10.0 mg/mL of amantadine hydrochloride from Oral Solution in water

Sample solution: Transfer 25 mL of Sample stock solution, equivalent to 250 mg of amantadine hydrochloride, and 10 mL of 5 N sodium hydroxide solution to a separatory funnel. Add 25 mL of Internal standard solution and shake for 10 min. Collect the upper layer of n-heptane and swirl with anhydrous sodium sulfate to remove traces of water.

Chromatographic system: Proceed as directed in the Assay.

4.2 System suitability

Sample: Standard solution

[Note-The relative retention times for adamantane and amantadine are 0.7 and 1.0, respectively.]

4.3 Suitability requirements

Relative standard deviation: NMT 3.0% for the peak response ratio of amantadine and adamantane

4.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual unspecified impurity in the portion of Oral Solution taken:

Result = (R_u/R_s) × (C_s/C_u) × 100

R_u = peak response ratio of any individual unspecified impurity to adamantane from the Sample solution

R_s = peak response ratio of amantadine to adamantane from the Standard solution

C_s = concentration of USP Amantadine Hydrochloride RS in the Standard stock solution (mg/mL)

C_u = nominal concentration of amantadine hydrochloride in the Sample stock solution (mg/mL)

Acceptance criteria: see Table 2.

Table 2

^a Process impurity included in the table for identification only. Process impurities are controlled in the drug substance, and are not to be reported or included in the total impurities for the drug product.

5 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Amantadine Hydrochloride RS

USP Amantadine Related Compound A RS

1-Chloroadamantane.

C₁₀H₁₅Cl170.68

USP Amantadine Related Compound B RS

N-(Adamantan-1-yl)acetamide.

C₁₂H₁₉NO 193.29