Amantadine Hydrochloride

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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C₁₀H₁₇N·HCl 187.71

Tricyclo[3.3.1.13,7]decan-1-amine, hydrochloride;

1-Adamantanamine hydrochloride CAS RN®: 665-66-7; UNII: M6Q1EO9TD0.

1 DEFINITION

Amantadine Hydrochloride contains NLT 98.0% and NMT 102.0% of amantadine hydrochloride (C₁₀H₁₇N·HCl).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A, 197K, or (ERR 1-Sep-2023) 197S

Procedure for 197S (ERR 1-Sep-2023)

Cell: 1 mm

Sample solution: 50 mg in 10 mL of 0.1 N hydrochloric acid. Filter, transfer the filtrate to a suitable separator, add 1 mL of 5 N sodium hydroxide, and extract with 5 mL of methylene chloride.

Acceptance criteria: Meets the requirements

B. The retention time of the amantadine peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C. Identification Tests-General 〈191〉, Chemical Identification Tests, Chloride

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 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.

Sample stock solution: 1 mg/mL of Amantadine Hydrochloride in water

Sample solution: Transfer 10 mL of Sample stock solution 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.

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, 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

Relative standard deviation: NMT 1.0% for the peak response ratio of amantadine to adamantane

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of amantadine hydrochloride (C₁₀H₁₇N·HCl) in the portion of Amantadine Hydrochloride 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 = concentration of Amantadine Hydrochloride in the Sample stock solution (mg/mL)

Acceptance criteria: 98.0%–102.0%

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 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.

Sample stock solution: 10 mg/mL of Amantadine Hydrochloride in water

Sample solution: Transfer 25 mL of Sample stock solution 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 to adamantane

4.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Amantadine Hydrochloride taken:

Result = (R_u/R_s) × (C_s/C_u) × 100

R_u = peak response ratio of any individual 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 = concentration of Amantadine Hydrochloride in the Sample stock solution (mg/mL)

Acceptance criteria: See Table 2.

Table 2

5 SPECIFIC TESTS

pH 〈791〉

Sample: 0.2 g/mL in water

Acceptance criteria: 3.0–5.5

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

SP Reference Standards 〈11〉

USP Amantadine Hydrochloride RS

USP Amantadine Related Compound A RS

1-Chloroadamantane.

C₁₀H₁₅Cl 170.68

USP Amantadine Related Compound B RS

N-(Adamantan-1-yl)acetamide.

C₁₂H₁₉NO 193.29