Artemether

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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C₁₆H₂₆O₅ 298.37

3,12-Epoxy-12H-pyrano [4,3-j]-1,2-benzodioxepin, decahydro-10-methoxy-3,6,9-trimethyl-, (3R,5aS, 6R,8aS, 9R, 10S,12R, 12aR);

(3R,5S,6R,8aS,9R, 10S, 12R, 12aR)-Decahydro-10-methoxy-3,6,9-trimethyl-3,12-epoxy-12H-pyrano [4,3-j]-1,2-benzodioxepin CAS RN^®: 71963-77-4; UNII: C7D6T3H22J.

1 DEFINITION

Artemether contains NLT 98.0% and NMT 102.0% of artemether (C16H2605).

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

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

Protect all solutions containing artemether from light.

Solution A: Acetonitrile and water (200:800)

Solution B: Acetonitrile and water (800:200)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (50:50)

Standard solution: 0.5 mg/mL of USP Artemether RS in Diluent. Sonicate to dissolve if necessary.

Sample solution: 0.5 mg/mL of Artemether in Diluent. Sonicate to dissolve if necessary.

Chromatographic system

(See Chromatography (621), System Suitability.)

Detector: UV 210 nm

Column: 4.6-mm × 15-cm; 1.8-µm packing L1

Temperatures

Autosampler: 5°

Column: 30°

Flow rate: 0.8 mL/min

Injection volume: 50 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of artemether (C₁₆H₂₆O₅) in the portion of Artemether taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of artemether from the Sample solution

r_S = peak response of artemether from the Standard solution 

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

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

Acceptance criteria: 98.0%-102.0%

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

Protect all solutions containing artemether from light.

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 5 µg/mL of USP Artemether RS in Diluent. Sonicate to dissolve if necessary.

Standard solution: 0.02 mg/mL of USP Artemether RS in Diluent. Sonicate to dissolve if necessary.

Sample solution: 10 mg/mL of Artemether in Diluent. Sonicate to dissolve if necessary.

System suitability

Samples: Sensitivity solution and Standard solution

Suitability requirements

Relative standard deviation: NMT 5%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Artemether taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of artemether from the Standard solution

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

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

^a 2-(4-Methyl-2-oxo-3-(3-oxobutyl) cyclohexyl)propanal.

^b The chromatographic system resolves two isomers. The sum of the values is reported.

^c (3R,5S,6R,8aS,9R,12R,12aR)-3,6,9-Trimethyldecahydro-3,12-epoxy [1,2]dioxepino [4,3-i]isochromen-10-ol.

^d (3R,5S,6R,8aS, 125, 12aR)-Octahydro-3,6-dimethyl-9-methylene-3,12-epoxy-12H-pyrano [4,3-j]-1,2-benzodioxepin-10(3H)-one.

^e (3aS,4R,6aS,7R,8S, 10R, 10aS)-8-Methoxy-4,7-dimethyldecahydrofuro[3,2-i]isochromen-10-yl acetate.

^f (3R,5aS,6R,8aS,9R, 10R, 12R, 12aR)-Decahydro-10-methoxy-3,6,9-trimethyl-3,12-epoxy-12H-pyrano [4,3-j]-1,2-benzodioxepin.

5 SPECIFIC TESTS

OPTICAL ROTATION TATION (781S), Procedures, Specific Rotation

Sample solution: 10 mg/mL in dehydrated alcohol

Acceptance criteria: +166° to +173° measured at 20°

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed, light-resistant containers. Store in a refrigerator.

USP REFERENCE STANDARDS (11).

USP Artemether RSA (USP 1-May-2023)