Miconazole Nitrate

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 · HNO₃ 479.14

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

1-[2,4-Dichloro-β-[(2,4-dichlorobenzyl)oxy]phenethyl]imidazole mononitrate   CAS RN®: 22832-87-7; UNII: VW4H1CYW1K.

1 DEFINITION

Miconazole Nitrate contains NLT 98.0% and NMT 102.0% of miconazole nitrate (C₁₈H₁₄Cl₄N₂O · HNO₃), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

Solution A: Methanol, water, and 1 M triethylammonium acetate (30:70:1)

Solution B: Acetonitrile, methanol, and 1 M triethylammonium acetate (25:75:0.2)

Mobile phase: See Table 1.

Table 1

Diluent: Methanol and water (70:30)

System suitability solution: 0.1 mg/mL of USP Miconazole Nitrate RS and 6 µg/mL of USP Miconazole Related Compound F RS in Diluent. Sonication may be needed to aid dissolution.

Standard solution: 0.1 mg/mL of USP Miconazole Nitrate RS in Diluent. Sonication may be needed to aid dissolution.

Sample solution: 0.1 mg/mL of Miconazole Nitrate in Diluent. Sonication may be needed to aid dissolution.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 215 nm
• Column: 4.6-mm × 10-cm; 2.6-µm packing L11
• Column temperature: 40°
• Flow rate: 0.8 mL/min
• Injection volume: 10 µL

System suitability

• Samples: System suitability solution and Standard solution
• [Note-The relative retention times for miconazole related compound F and miconazole are 0.96 and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 1.5 between miconazole related compound F and miconazole, System suitability solution
• Tailing factor: NMT 2.0, Standard solution
• Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of miconazole nitrate (C₁₈H₁₄Cl₄N₂O · HNO₃) in the portion of Miconazole Nitrate taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of miconazole from the Sample solution

rₛ = peak response of miconazole from the Standard solution

Cₛ = concentration of USP Miconazole Nitrate RS in the Standard solution (mg/mL)

Cᵤ = concentration of Miconazole Nitrate in the Sample solution (mg/mL)

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

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

Standard solution: 1.2 µg/mL each of USP Miconazole Nitrate RS, USP Econazole Nitrate RS, USP Miconazole Related Compound C RS, USP Miconazole Related Compound F RS, and USP Miconazole Related Compound I RS in Diluent

Sample solution: 600 µg/mL of Miconazole Nitrate in Diluent. Sonication may be needed to aid dissolution.

System suitability

• Sample: Standard solution
• [Note-See Table 2 for relative retention times.]
• Suitability requirements
• Resolution: NLT 1.5 between miconazole related compound C and miconazole related compound I; NLT 1.5 between miconazole related compound I and econazole; and NLT 1.5 between miconazole related compound F and miconazole
• Relative standard deviation: NMT 3.0% for miconazole

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of miconazole related compound C, miconazole related compound F, miconazole related compound I, or econazole nitrate in the portion of Miconazole Nitrate taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of miconazole related compound C, miconazole related compound F, miconazole related compound I, or econazole nitrate from the Sample solution

rₛ = peak response of miconazole related compound C, miconazole related compound F, miconazole related compound I, or econazole nitrate from the Standard solution

Cₛ = concentration of USP Miconazole Related Compound C RS, USP Miconazole Related Compound F RS, USP Miconazole Related Compound I RS, or USP Econazole Nitrate RS in the Standard solution (µg/mL)

Cᵤ = concentration of Miconazole Nitrate in the Sample solution (µg/mL)

Calculate the percentage of each specified and any individual unspecified impurity in the portion of Miconazole Nitrate taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of each specified and any individual unspecified impurity from the Sample solution

rₛ = peak response of miconazole from the Standard solution

Cₛ = concentration of USP Miconazole Nitrate RS in the Standard solution (µg/mL)

Cᵤ = concentration of Miconazole Nitrate in the Sample solution (µg/mL)

Acceptance criteria: See Table 2.

Table 2

ᵃ 1-(2,4-Dichlorophenyl)-2-(1H-imidazol-1-yl)ethanol.

ᵇ 2-(3-{2-[(2,4-Dichlorobenzyl)oxy]-2-(2,4-dichlorophenyl)ethyl}-1H-imidazol-3-ium-1-yl)-2-methylpropanoate.

ᶜ 1-[2-(Benzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole.

ᵈ 1-{2-[(2,6-Dichlorobenzyl)oxy]-2-(2,4-dichlorophenyl)ethyl}-1H-imidazole.

ᵉ 1-{2-[(2,5-Dichlorobenzyl)oxy]-2-(2,4-dichlorophenyl)ethyl}-1H-imidazole.

5 SPECIFIC TESTS

Change to read:

5.1 Optical Rotation 〈781A〉, Procedures, Angular Rotation

Sample solution: 10 mg/mL of Miconazole Nitrate in methanol

Acceptance criteria: −0.10° to +0.10° at 20°

5.2 Loss on Drying 〈731〉

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

6.1 Packaging and Storage

Preserve in well-closed containers, protected from light. Store at controlled room temperature.

6.2 USP Reference Standards 〈11〉

USP Econazole Nitrate RS

USP Miconazole Nitrate RS

USP Miconazole Related Compound C RS

2-[(2,4-Dichlorobenzyl)oxy]-2-(2,4-dichlorophenyl)ethan-1-amine hydrochloride.

C₁₅H₁₃Cl₄NO · HCl 401.53

USP Miconazole Related Compound F RS

1-{2-[(3,4-Dichlorobenzyl)oxy]-2-(2,4-dichlorophenyl)ethyl}-1H-imidazole.

C₁₈H₁₄Cl₄N₂O 416.13

USP Miconazole Related Compound I RS

1-{2-[(2-Chlorobenzyl)oxy]-2-(2,4-dichlorophenyl)ethyl}-1H-imidazole mononitrate.

C₁₈H₁₅Cl₃N₂O · HNO₃ 444.69