Oxiconazole 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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C₁₈H₁₃CI₄N₃O·HNO₃ 492.14

Ethanone, 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-, O-[(2,4-dichlorophenyl)methyl]oxime, (Z)-, mononitrate;

2',4'-Dichloro-2-imidazol-1-ylacetophenone (Z)-[O-(2,4-dichlorobenzyl)oxime], mononitrate CAS RN^®: 64211-46-7; UNII: RQ8UL4C17S.

1 DEFINITION

Oxiconazole Nitrate contains NLT 98.0% and NMT 102.0% of oxiconazole nitrate (C₁₈H₁₃CI₄N₃O·HNO₃), calculated on the dried basis.

2 IDENTIFICATION

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

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

3 ASSAY

3.1 PROCEDURE

Solution A: 2.72 g/L of monobasic potassium phosphate in water

Mobile phase: Acetonitrile and Solution A (44:56). Adjust with phosphoric acid to a pH of 4.4.

Diluent: Acetonitrile and water (50:50)

Standard solution: 0.2 mg/mL of USP Oxiconazole Nitrate RS in Diluent. Sonicate, if necessary, to dissolve.

Sample solution: 0.2 mg/mL of Oxiconazole Nitrate in Diluent. Sonicate, if necessary, to dissolve.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 15-cm; 3-µm packing L1

Column temperature: 40°

Flow rate: 1.2 mL/min

Injection volume: 10 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 oxiconazole nitrate (C₁₈H₁₃CI₄N₃O·HNO₃) in the portion of Oxiconazole Nitrate taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of oxiconazole from the Sample solution

r_S = peak response of oxiconazole from the Standard solution

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

C_U = concentration of Oxiconazole 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

[NOTE-Protect solutions containing oxiconazole from light and store in a refrigerator until ready to use.]

Buffer: 2.64 g/L of dibasic ammonium phosphate in water. Adjust with phosphoric acid to a pH of 7.0.

Solution A: Acetonitrile and Buffer (30:70)

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Standard stock solution 1: 1 mg/mL of USP Oxiconazole Nitrate RS in acetonitrile

Standard stock solution 2: 0.1 mg/mL each of USP Oxiconazole Related Compound A RS, USP Oxiconazole Related Compound B RS, USP Oxiconazole Related Compound C RS, USP Oxiconazole Related Compound D RS, and USP Oxiconazole Related Compound E RS in acetonitrile

Sensitivity solution: 0.5 µg/mL of USP Oxiconazole Nitrate RS from Standard stock solution 1 in acetonitrile

Standard solution: 0.002 mg/mL of USP Oxiconazole Nitrate RS from Standard stock solution 1 and 0.002 mg/mL each of USP Oxiconazole Related Compound A RS, USP Oxiconazole Related Compound B RS, USP Oxiconazole Related Compound C RS, USP Oxiconazole Related Compound D RS, and USP Oxiconazole Related Compound E RS from Standard stock solution 2 in acetonitrile

Sample solution: 1 mg/mL of Oxiconazole Nitrate in acetonitrile

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 250 nm for oxiconazole related compound C and 225 nm for the remaining impurities

Column: 4.6-mm x 25-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: Sensitivity solution and Standard solution

Suitability requirements

Resolution: NLT 1.2 between oxiconazole related compound A and oxiconazole determined at 225 nm, Standard solution

Relative standard deviation: NMT 5.0% for the oxiconazole peak determined at 225 nm, Standard solution

Signal-to-noise ratio: NLT 10 determined at 225 nm, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of oxiconazole related compound A, B, C, D, and E in the portion of Oxiconazole Nitrate taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of the relevant oxiconazole related compound from the Sample solution

r_S = peak response of the relevant oxiconazole related compound from the Standard solution

C_S = concentration of the corresponding USP Reference Standard in the Standard solution (mg/mL)

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

Calculate the percentage of any other individual impurity in the portion of Oxiconazole Nitrate taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of any other individual impurity from the Sample solution

r_S = peak response of oxiconazole from the Standard solution

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

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

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

Table 2

5 SPECIFIC TESTS

5.1 LOSS ON DRYING (731)

Analysis: Dry at 105° for 4 h.

Acceptance criteria: NMT 1.0%

5.2 PH (791)

Sample: 10 mg/mL suspension in water

Acceptance criteria: 3.0-4.0

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight containers, and store at room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Oxiconazole Nitrate RS

USP Oxiconazole Related Compound A RS

2',4'-Dichloro-2-imidazol-1-ylacetophenone (E)-[O-(2,4-dichlorobenzyl)oxime], mononitrate.

C₁₈H₁₃CI₄N₃O 429.14

USP Oxiconazole Related Compound B RS

(Z)-1-(2,4-Dichlorophenyl)-2-(1H-imidazol-1-yl)ethanone oxime.

C₁₁H₉CI₂N₃O 270.11

USP Oxiconazole Related Compound C RS

1-(2,4-Dichlorophenyl)-2-(1H-imidazol-1-yl)ethan-1-one hydrochloride.

C₁₁H₈CI₂N₂O·HCI 291.56

USP Oxiconazole Related Compound D RS

(2,4-Dichlorophenyl)methanol.

C₇H₆CI₂O 177.02

USP Oxiconazole Related Compound E RS

2,4-Dichlorobenzyl chloride.

C₇H₅CI₃ 195.47(USP 1-May-2022)