Amodiaquine 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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C₂₀H₂₂ClN₃O · 2HCl · 2H₂O 464.81

C₂₀H₂₂ClN₃O · 2HCl 428.79

Phenol, 4-[(7-chloro-4-quinolinyl)amino]-2-[(diethylamino)-methyl]-, dihydrochloride, dihydrate;

4-[(7-Chloro-4-quinolyl)amino]-α-(diethylamino)-o-cresol dihydrochloride dihydrate CAS RN®: 6398-98-7; UNII: K6PW2S574L.

Anhydrous CAS RN®: 69-44-3; UNII: HOE64181MP.

1 DEFINITION

Amodiaquine Hydrochloride contains NLT 97.0% and NMT 103.0% of amodiaquine hydrochloride (C₂₀H₂₂ClN₃O · 2HCl), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

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

Sample: Dissolve 20 mg of Amodiaquine Hydrochloride in 10 mL of water in a separator. Add 1 mL of ammonium hydroxide, and extract by shaking with 25 mL of chloroform. Draw off and evaporate the chloroform extract, and dry the residue at 105° for 2 h.

Acceptance criteria: Meets the requirements

Change to read:

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U (CN 1-May-2020)

Sample solution: 10 μg/mL in dilute hydrochloric acid (1 in 100)

Acceptance criteria: Meets the requirements

C. Identification Tests-General, Chloride〈191〉: Meets the requirements

D. 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

Buffer: 6.8 g/L of monobasic potassium phosphate in water. Add 1.0 mL of perchloric acid to each 1 L of solution, adjust with phosphoric acid to a pH of 2.5 ± 0.5, and pass through a filter of 0.45-μm pore size.

Mobile phase: Methanol and Buffer (22:78)

System suitability solution: 0.15 mg/mL of USP Amodiaquine Hydrochloride RS and 0.15 mg/mL of USP Chloroquine Phosphate RS in water

Standard solution: 0.15 mg/mL of USP Amodiaquine Hydrochloride RS in water

Sample solution: 0.15 mg/mL in water

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 224 nm

Column: 4.6-mm × 10-cm; 5-μm packing L1

Column temperature: 25° ± 5°

Flow rate: 1.2 mL/min

Injection volume: 10 μL

3.3 System suitability

Sample: System suitability solution

[Note - The relative retention times for chloroquine phosphate and amodiaquine hydrochloride are 0.8 and 1.0, respectively.]

3.4 Suitability requirements

Resolution: NLT 1.5 between amodiaquine hydrochloride and chloroquine phosphate

Tailing factor: NMT 1.5 for amodiaquine hydrochloride and chloroquine phosphate

Relative standard deviation: NMT 2.0% for amodiaquine hydrochloride and chloroquine phosphate

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of amodiaquine hydrochloride (C₂₀H₂₂ClN₃O · 2HCl) in the portion of Amodiaquine Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = response from the Sample solution

r_S = response from the Standard solution

C_S = concentration of USP Amodiaquine Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Amodiaquine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 97.0%–103.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%

Organic Impurities

Buffer, Mobile phase, System suitability solution, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Amodiaquine Hydrochloride taken:

Result = (r_U/r_T) × 100

r_U = response of each impurity from the Sample solution

r_T  = sum of the responses from the Sample solution

Acceptance criteria

Individual impurity: NMT 0.5%

5 SPECIFIC TESTS

Water Determination, Method I〈921〉: 7.0%–9.0%

Completeness of Solution 〈641〉: A solution of 200 mg in 10 mL of water is clear.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Amodiaquine Hydrochloride RS

USP Chloroquine Phosphate RS