Econazole Nitrate

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

Econazole Nitrate contains NLT 98.0% and NMT 102.0% of econazole nitrate (C₁₈H₁₅Cl₃N₂O · HNO₃), calculated on the dried basis.

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.

C.

Sample solution: 10 mg with 5 mL of water

Analysis: Shake the Sample solution, and cool the resulting suspension in ice. Keeping the suspension cool, add 0.4 mL of potassium chloride solution (1 in 10), 0.1 mL of diphenylamine TS, and, dropwise with shaking, 5 mL of sulfuric acid.

Acceptance criteria: An intense blue color develops.

3 ASSAY

Procedure

Solution A: 0.77 g/L of ammonium acetate in water

Solution B: Methanol and Solution A (20:80)

Solution C: Acetonitrile and methanol (60:40)

Mobile phase: See Table 1.

Table 1

Diluent: Methanol and water (40:60)

Standard solution: 0.4 mg/mL of USP Econazole Nitrate RS in Diluent. [Note—Sonication may be needed to dissolve the Standard.]

Sample solution: 0.4 mg/mL of Econazole Nitrate in Diluent. [Note—Sonication may be needed to dissolve the sample.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 225 nm

Column: 4.6-mm × 10-cm; 3-μm packing L1

Column temperature: 35°

Flow rate: 1.5 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of econazole nitrate (C₁₈H₁₅Cl₃N₂O · HNO₃) in the portion of Econazole Nitrate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U= peak response of econazole from the Sample solution

r_S= peak response of econazole from the Standard solution

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

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

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Mobile phase and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.02 mg/mL each of USP Econazole Related Compound A RS, USP Econazole Related Compound B RS, and USP

Econazole Related Compound C RS, and 0.01 mg/mL of USP Econazole Nitrate RS in methanol

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

System suitability

Sample: Standard solution

[Note—See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 3.0 between econazole related compound C and econazole

Relative standard deviation: NMT 3% for econazole related compound A, econazole related compound B, econazole related compound C, and econazole

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of econazole related compound A, econazole related compound B, or econazole related compound C in the portion of Econazole Nitrate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U= peak response of econazole related compound A, econazole related compound B, or econazole related compound C from the Sample solution

r_S= peak response of econazole related compound A, econazole related compound B, or econazole related compound C from the Standard solution

C_S = concentration of USP Econazole Related Compound A RS, USP Econazole Related Compound B RS, or USP Econazole Related Compound C RS in the Standard solution (mg/mL)

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

Calculate the percentage of any other unspecified impurities in the portion of Econazole Nitrate taken:

Result = ((r_U/r_S) × (C_S/C_U) × 100

r_U= peak response of each impurity from the Sample solution

r_S= peak response of econazole from the Standard solution

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

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

Acceptance criteria: See Table 2.

Table 2

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry at 105° to constant weight.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, protected from light.

Change to read:

USP Reference Standards 〈11〉

USP Econazole Nitrate RS

USP Econazole Related Compound A RS

Deschlorobenzyl econazole;

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

C₁₁H10Cl₂N₂O 257.12

USP Econazole Related Compound B RS

Econazole amine;

2-[(4-Chlorobenzyl)oxy]-2-(2,4-dichlorophenyl)ethanamine nitrate.

C₁₅H₁₄Cl₃NO · HNO 393.65

USP Econazole Related Compound C RS

Econazole quarternary salt;

1-(4-Chlorobenzyl)-3-{2-[(4-chlorobenzyl)oxy]-2-(2,4-dichlorophenyl)ethyl}-1H-imidazol-3-ium chloride.

C₂₅H₂₁Cl₅N₂O 542.71 (ERR 1-Sep-2022)