Miconazole

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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C₁₈H₁₄Cl₄N₂O 416.13

1H-Imidazole, 1-2-[(2,4-dichlorophenyl)-2-[(2,4-dichlorophenyl)]methoxy]ethyl]-, (±)-;

(±)-1-[2,4-Dichloro-β-[(2,4-dichlorobenzyl)oxy] phenethyl]imidazole  CAS RN®: 22916-47-8; UNII: 7NNO0D7S5M.

1 DEFINITION

Miconazole contains NLT 98.0% and NMT 102.0% of miconazole (C₁₈H₁₄Cl₄N₂O), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

B.

Sample solution: Dissolve 40 mg in 50 mL of isopropyl alcohol in a 100-mL volumetric flask, and add 10 mL of 0.1 N hydrochloric acid. Dilute with isopropyl alcohol to volume.

Acceptance criteria: The UV absorption spectrum of the Sample solution exhibits maxima and minima at the same wavelengths as that of a similar solution of USP Miconazole RS, concomitantly measured.

3 ASSAY

3.1 Procedure

Sample solution: 300 mg of Miconazole in 40 mL of glacial acetic acid. Add 4 drops of p-naphtholbenzein TS.

Titrimetric system

Mode: Direct titration

Titrant: 0.1 N perchloric acid VS

Endpoint detection: Visual

Analysis: Titrate the Sample solution with Titrant to a green endpoint. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 41.61 mg of miconazole (C₁₈H₁₄Cl₄N₂O).

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

4 IMPURITIES

4.1 Residue on Ignition 〈281〉

NMT 0.2%

4.2 Organic Impurities

Standard solution A: 10 mg/mL of USP Miconazole RS in chloroform

Standard solution B: 100 µg/mL of USP Miconazole RS from Standard solution A in chloroform

Sample solution: 10 mg/mL in chloroform

Chromatographic system

• (See Chromatography 〈621〉, Thin-Layer Chromatography.)
• Mode: TLC
• Adsorbent: 0.25-mm layer of chromatographic silica gel mixture
• Application volume: 5 µL
• Developing solvent system: n-Hexane, chloroform, methanol, and ammonium hydroxide (60:30:10:1)

Analysis

Samples: Standard solution A, Standard solution B, and Sample solution

Apply the Samples separately to the starting line of the plate. Develop the chromatogram in a suitable chamber with freshly prepared Developing solvent system until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, and allow the solvent to evaporate. Expose the plate to iodine vapors in a closed chamber for 30 min, and locate the spots.

Acceptance criteria: The R_F value of the principal spot from the Sample solution corresponds to that from Standard solution A, and any other spot from the Sample solution does not exceed, in size or intensity, the principal spot from Standard solution B (1.0%).

5 SPECIFIC TESTS

5.1 Loss on Drying 〈731〉

Analysis: Dry a sample under vacuum at 60° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, protected from light. Store at 25°, excursions permitted between 15° and 30°.

USP Reference Standards 〈11〉

USP Miconazole RS