Tioconazole

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

C₁₆H1₃CI₃N₂OS            387.71

1H-Imidazole, 1-[2-[(2-chloro-3-thienyl)methoxy]-2-(2,4-dichlorophenyl)ethyl]-;

1-[2,4-Dichloro-[β-(2-chloro-3-thenyl)-oxy]phen ethylimidazole CAS RN^®: 65899-73-2; UNII: S57Y5X1117.

1 DEFINITION

Tioconazole contains NLT 97.0% and NMT 103.0% of C₁₆H1₃CI₃N₂OS.

2 IDENTIFICATION

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

B. PROCEDURE

Standard solution: 50 mg/mL of USP Tioconazole RS in methanol

Sample solution: 50 mg/mL of Tioconazole in methanol

Developing solvent system: Chloroform, methanol, and glacial acetic acid (40:5:1)

Visualizing solution: Dissolve 0.85 g of Bismuth subnitrate in 10 ml of glacial acetic acid, and dilute with water to 50 mL. Mix 10 mL of this solution, 50 mL of potassium iodide solution (2 in 25), and 20 mL of glacial acetic acid, and dilute to 100 mL..

Chromatographic system

(See Chromatography (621), Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 10 µL

Analysis

Samples: Standard solution and Sample solution

Develop the chromatogram until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber and locate the spots on the plate by viewing under short- and long-wavelength UV light after drying the plate at 80° for 5 min. Spray the plate with Visualizing solution, air-dry for 2 min, and overspray with sodium nitrite solution (1 in 20). Air-dry the plate for 5 min, and examine it for brown spots on a pale yellow background.

Acceptance criteria: The R_F value of the principal spot from the Sample solution corresponds to that from the Standard solution.

C. The retention time of the major peak for tioconazole of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Mobile phase: Acetonitrile, methanol, and water (44:40:28). Degas the solution, and add 2.0 mL of ammonium hydroxide to 1120 mL of Mobile phase. [NOTE-Prepare the Mobile phase fresh daily.]

Standard solution: 200 µg/mL of USP Tioconazole RS in methanol

Sample solution: 200 µg/mL of Tioconazole in methanol

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 219 nm

Column: 5-mm x 25-cm; packing L1 with a precolumn containing packing L4 installed between the pump and the injector. [NOTE-Replace the precolumn daily.]

Flow rate: Adjust to obtain a retention time of between 12 and 17 min for tioconazole.

Injection size: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 1000 theoretical plates, determined from the analyte peak

Tailing factor: NMT 2.0 for the analyte peak

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₆H1₃CI₃N₂OS in the Tioconazole taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 97.0%-103.0%

4 IMPURITIES

4.1 INORGANIC IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.2%

CHLORIDE AND SULFATE, Chloride (221): A 0.7-g portion dissolved in methanol shows no more chloride than corresponds to 0.50 mL of 0.020 N hydrochloric acid (0.05%).

4.2 ORGANIC IMPURITIES

PROCEDURE

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

Standard solution: Dissolve 1 mg each of USP Tioconazole Related Compound A RS, USP Tioconazole Related Compound B RS, and USP Tioconazole Related Compound C RS in 15.0 mL of methanol, and shake until the contents are completely dissolved.

Sample solution: Dissolve 100 mg of Tioconazole in 15.0 mL of methanol, and shake until the substance is completely dissolved.

Analysis

Samples: Standard solution and Sample solution

Calculate, in turn, the percentages of 1-[2,4-dichloro-β-[(3-thenyl)-oxy]phenethyl]imidazole hydrochloride (tioconazole related compound A), 1-[2,4-dichloro-β-[(2,5-dichloro-3-thenyl)-oxy)phenethyl]imidazole hydrochloride (tioconazole related compound B), and 1-[2,4-dichloro-β-[(5-bromo-2-chloro-3-thenyl)-oxy]phenethyl]imidazole hydrochloride (tioconazole related compound C) in the portion of Tioconazole taken:

                          Result = (r_U/r_S) x (W_l/W_U) x 100

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

r_S = peak response of the related compound from the Standard solution s

W_l = weight of the respective USP Reference Standard taken to prepare the Standard solution (mg)

W_U = weight of Tioconazole taken to prepare the Sample solution (mg)

Acceptance criteria: The limit of each related compound is NMT 1.0%.

5 SPECIFIC TESTS

WATER DETERMINATION, Method (921): NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

Change to read:

USP REFERENCE STANDARDS (11)

USP Tioconazole RS

USP Tioconazole Related Compound A RS

1-[2,4-Dichloro-β-[(3-thenyl)-oxy]phenethyl]imidazole hydrochloride.

C₁₆H₁₄CI₂N₂OS · HCI         ^▲389.72 _{▲(ERR 1-Jul-2023)}

USP Tioconazole Related Compound B RS

1-[2,4-Dichloro-β-[(2,5-dichloro-3-thenyl)oxy]phenethyl]imidazole hydrochloride.

C₁₆H₁₂CI₄N₂OS · HCI            ^▲458.60 _{▲(ERR 1-Jul-2023)}

USP Tioconazole Related Compound C RS

1-[2,4-Dichloro-β-[(5-bromo-2-chloro-3-thenyl)-oxy]-phenethyllimidazole hydrochloride.

^▲C₁₆H₁₄BrCI₃N₂OS · HCI          503.06_{▲(ERR 1-Jul-2023)}