Mefloquine 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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1 DEFINITION

Mefloquine Hydrochloride contains NLT 98.0% and NMT 102.0% of C₁₇H₁₆F₆N₂O · HCl, calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

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

B. Identification Tests—General, Chloride〈191〉

3 ASSAY

Procedure

Solution A: 1.5 g/L of sodium hydrogen sulfate in water

Mobile phase: Dissolve 1 g of tetraheptylammonium bromide in a 1000-mL mixture of acetonitrile, methanol, and Solution A (2:1:2).

System suitability solution: 4 μg/mL each of USP Mefloquine Hydrochloride RS and USP Mefloquine Related Compound A RS in Mobile phase

Standard solution: 0.2 mg/mL of USP Mefloquine Hydrochloride RS in Mobile phase

Sample solution: 0.2 mg/mL of Mefloquine Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Guard column: 4-mm × 3-cm; C18 (recommended)

Column: 4.0-mm × 25-cm; 5-μm packing L1

Column temperature: 25°

Flow rate: 0.8 mL/min

Injection size: 20 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for mefloquine related compound A and mefloquine are about 0.7 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between mefloquine related compound A and mefloquine, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of mefloquine hydrochloride (C₁₇H₁₆F₆N₂O · HCl) in the portion of Mefloquine Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of mefloquine from the Sample solution

r_S = peak response of mefloquine from the Standard solution

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

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

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Mobile phase: Dissolve 1 g of tetraheptylammonium bromide in a 1-L mixture of a 1.5-g/L solution of sodium hydrogen sulfate, acetonitrile, and methanol (2:2:1).

System suitability solution: 4 μg/mL each of USP Mefloquine Hydrochloride RS and USP Mefloquine Related Compound A RS in Mobile phase. [Note—Mefloquine related compound A is threo-mefloquine.]

Sample stock solution: 4 mg/mL of Mefloquine Hydrochloride in Mobile phase

Sample solution: 4 μg/mL from the Sample stock solution in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Guard column: 4-mm × 2.5-cm; 5-μm packing L1

Column: 4.0-mm × 25-cm; 5-μm packing L1

Flow rate: 0.8 mL/min

Injection size: 20 μL. [Note—Equilibrate the column with Mobile phase at a flow rate of 0.8 mL/min for 30 min.]

System suitability

Sample: System suitability solution

[Note—The relative retention times for mefloquine related compound A and mefloquine are about 0.7 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between mefloquine related compound A and mefloquine

Relative standard deviation: NMT 2.0%

Analysis

Samples: Sample stock solution and Sample solution

Record the chromatogram for a time that is 10 times the retention time of the main peak.

Acceptance criteria: The response of the mefloquine related compound A peak in the Sample stock solution is NMT twice the area of the main peak of the Sample solution (0.2%). The response of any other individual peak, other than the main peak of the Sample stock solution, is NMT that of the main peak of the Sample solution (0.1%); and the sum of the responses of any such peaks of the Sample stock solution is NMT five times the response of the main peak of the Sample solution (0.5%). [Note—Exclude the main peak and any other peak producing a response of less than 0.2 times (0.02%) the main peak of the Sample solution.]

5 SPECIFIC TESTS

Optical Rotation, Specific Rotation〈781S〉

Sample solution: 50 mg/mL in methanol

Acceptance criteria: –0.2° to +0.2°

Water Determination, Method I〈921〉: NMT 3.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store between 15° and 30°.

USP Reference Standards 〈11〉

USP Mefloquine Hydrochloride RS

USP Mefloquine Related Compound A RS threo-Mefloquine.