Lumefantrine

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

Lumefantrine contains NLT 98.0% and NMT 102.0% of lumefantrine (C₃₀H₃₂Cl₃NO).

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

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

3 ASSAY

Procedure

Buffer: Dissolve 5.65 g of sodium 1-hexanesulfonate and 2.75 g of monobasic sodium phosphate in 900 mL of water. Adjust with phosphoric acid to a pH of 2.3 before dilution with water to a final volume of 1000 mL.

Solution A: Acetonitrile and Buffer (300:700)

Solution B: Acetonitrile and 2-propanol (540:460)

Mobile phase: See Table 1.

Table 1

System suitability stock solution: 10 μg/mL of USP Lumefantrine Related Compound A RS prepared as follows. Transfer a suitable quantity of USP Lumefantrine Related Compound A RS to a volumetric flask, dissolve in 10% volume dichloromethane, and dilute with acetonitrile to volume.

System suitability solution: 1 mg/mL of USP Lumefantrine RS and 1 μg/mL of USP Lumefantrine Related Compound A RS prepared as follows. Transfer 10 mg of USP Lumefantrine RS to a 10-mL volumetric flask, and dissolve in 1 mL of dichloromethane. Add 1.0 mL of the System suitability stock solution, and dilute with acetonitrile to volume.

Standard solution: 1 mg/mL of USP Lumefantrine RS prepared as follows. Transfer a suitable quantity of USP Lumefantrine RS to a volumetric flask, dissolve in 10% volume of dichloromethane, and dilute with acetonitrile to volume.

Sample solution: 1 mg/mL of Lumefantrine prepared as follows. Transfer a suitable quantity of Lumefantrine to a volumetric flask, dissolve in 10% volume of dichloromethane, and dilute with acetonitrile to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 265 nm

Column: 4.6-mm × 50-mm; 1.8-μm packing L1

Column temperature: Beginning of column, 50°; end of column, 35°

Flow rate: 2.5 mL/min

Injection volume: 2.5 μL

Run time: 20 min

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for lumefantrine related compound A and lumefantrine are 0.9 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.3 between lumefantrine and lumefantrine related compound A, System suitability solution

Tailing factor: NMT 2.1, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of lumefantrine (C₃₀H₃₂Cl₃NO) in the portion of Lumefantrine taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

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

Acceptance criteria: 98.0%–102.0%

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Buffer, Solution A, Solution B, Mobile phase, System suitability stock solution, System suitability solution, Sample solution,

Chromatographic system, and System suitability: Proceed as directed in the Assay.

Standard stock solution: 50 μg/mL of USP Lumefantrine RS prepared as follows. Transfer a suitable quantity of USP Lumefantrine RS into a volumetric flask, dissolve in 10% volume of dichloromethane, and dilute with acetonitrile to volume.

Standard solution: 1 μg/mL of USP Lumefantrine RS in acetonitrile from the Standard stock solution

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of desbutyl lumefantrine or any other impurity in the portion of Lumefantrine taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak response of desbutyl lumefantrine or any other impurity from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

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

F = relative response factor

Acceptance criteria: See Table 2. Disregard any peak less than 0.05%.

Table 2

^a (Z)-2-(Butylamino)-1-(2,7-dichloro-9-(4-chlorobenzylidene)-9H-fluoren-4-yl)ethanol.

5 SPECIFIC TESTS

Clarity of Solution

Hydrazine sulfate solution: Transfer 1.0 g of hydrazine sulfate to a 100-mL volumetric flask, and dissolve in and dilute with water to volume.

Allow to stand for 4–6 h before use.

Methenamine solution: Transfer 2.5 g of methenamine to a 100-mL glass-stoppered flask, add 25 mL of water, insert the glass stopper, and mix to dissolve.

Primary opalescent suspension: Transfer 25.0 mL of Hydrazine sulfate solution to the Methanamine solution in the 100-mL glass-stoppered flask. Allow to stand for 24 h. This suspension is stable for 2 months, provided it is stored in a glass container free from surface defects.

The suspension must not adhere to the glass and must be well mixed before use.

Stock opalescence suspension: Transfer 15.0 mL of the Primary opalescent suspension to a 1000-mL volumetric flask, and dilute with water to volume. This suspension should not be used beyond 24 h after preparation.

Sample solution: Dissolve 1.0 g of Lumefantrine in dichloromethane, and dilute with dichloromethane to 10.0 mL.

Standard suspension: Transfer 5.0 mL of Stock opalescence suspension to a 100-mL volumetric flask, and dilute with water to volume.

Prepare only if the Sample solution is not as clear as water or dichloromethane.

Analysis

Samples: Sample solution, Standard suspension, water, and dichloromethane

Transfer a sufficient portion of the Sample solution to a test tube of colorless, transparent, neutral glass with a at base and an internal diameter of 15–25 mm to obtain a depth of 40 mm. Similarly transfer portions of Standard suspension and dichloromethane to separate matching test tubes. Compare the Sample solution, Standard suspension, water, and dichloromethane in diffused daylight, viewing vertically against a black background. The diffusion of light must be such that the Standard suspension can readily be distinguished from dichloromethane. If the Sample solution is as clear as water or dichloromethane, it is not necessary to prepare the

Standard suspension.

Acceptance criteria: The Sample solution shows the same or more clarity than water, dichloromethane, or the Standard suspension.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at room temperature.

USP Reference Standards 〈11〉

USP Lumefantrine RS

USP Lumefantrine Related Compound A RS

(RS,Z)-2-(Dibutylamino)-2-(2,7-dichloro-9-(4-chlorobenzylidene)-9H-fluoren-4-yl)ethanol.

C₃₀H₃₂Cl₃NO 528.94