Triclabendazole

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

C₁₄H₉Cl₃N₂OS     359.65

1H-Benzimidazole, 6-chloro-5-(2,3-dichlorophenoxy)-2-(methylthio)-; 5-Chloro-6-(2,3-dichlorophenoxy)-2-(methylthio)-1H-benzimidazole CAS RN: 68786-66-3; UNII: 4784C8E03O.

1 DEFINITION

Triclabendazole contains NLT 99.0% and NMT 101.0% of triclabendazole (C₁₄H₉Cl₃N₂OS), calculated on the dried basis.

2 IDENTIFICATION

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

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard stock solution as obtained in the test for Organic Impurities.

3 ASSAY

PROCEDURE

Sample solution: 5.6 mg/mL of Triclabendazole in glacial acetic acid. Sonicate if necessary to dissolve.

Titrant: 0.1 N perchloric acid

Analysis

Titrate with Titrant, determining the endpoint potentiometrically. Perform a blank determination and make any necessary correction (see Titrimetry (541)).

Calculate the percentage of triclabendazole (C₁₄H₉Cl₃N₂OS) in the portion of Triclabendazole taken:

Result = {[(V_S − V_B ) × N × F]/W} × 100

V_S = sample titrant volume (mL)

V_B = blank titrant volume (mL)

N = actual normality of titrant (mEq/mL)

F = equivalency factor, 359.7 mg/mEq

W = sample weight (mg)

Acceptance criteria: 99.0%–101.0% on the dried basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

ORGANIC IMPURITIES

Protect the solutions containing triclabendazole from light.

Buffer: 0.77 g/L of ammonium acetate in water prepared as follows. Dissolve 0.77 g of ammonium acetate in about 800 mL of water. Add 1 mL of triethylamine. Adjust with glacial acetic acid to a pH of 4.5 and dilute with water to volume.

Mobile phase: Acetonitrile and Buffer (54:46)

System suitability solution: 2 mg/mL of USP Triclabendazole RS and 0.012 mg/mL each of USP Triclabendazole Related Compound A RS.

USP Triclabendazole Related Compound B RS, and USP Triclabendazole Related Compound D RS prepared as follows. To a suitable amount of USP Triclabendazole RS, USP Triclabendazole Related Compound A RS, USP Triclabendazole Related Compound B RS, and USP Triclabendazole Related Compound D RS add about 10% of the flask volume of acetonitrile to dissolve. Dilute with Mobile phase to final volume.

Standard stock solution: 2 mg/mL of USP Triclabendazole RS in Mobile phase prepared as follows. Transfer a suitable amount of Triclabendazole to a suitable volumetric flask and add about 40% of the flask volume of acetonitrile to dissolve. Dilute with Mobile phase to volume.

Standard solution: 0.004 mg/mL of USP Triclabendazole RS in Mobile phase from Standard stock solution

Sensitivity solution: 0.001 mg/mL of USP Triclabendazole RS in Mobile phase from Standard solution

Sample solution: 2 mg/mL of Triclabendazole prepared as follows. Transfer a suitable amount of Triclabendazole to a suitable volumetric flask and add about 40% of the flask volume of acetonitrile to dissolve. Dilute with Mobile phase to final volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 305 nm

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

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 4.5 times the retention time of triclabendazole

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

[Note—The relative retention times for triclabendazole related compound A, triclabendazole related compound B, and triclabendazole are 0.55, 0.63, and 1.0 respectively.]

Suitability requirements

Resolution: NLT 1.5 between triclabendazole related compound A and triclabendazole related compound B, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Triclabendazole taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × 100

r_u = peak response of any individual impurity from the Sample solution

r_s = peak response of triclabendazole from the Standard solution

C_s = concentration of USP Triclabendazole RS in the Standard solution (mg/mL)

C_u = concentration of triclabendazole in the Sample solution (mg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

Table 1

5 ADDITIONAL REQUIREMENTS

Loss on Drying 〈731〉

Analysis: Dry the sample at 105°–110° for 6 h under vacuum.

Acceptance criteria: NMT 0.5%

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

USP Reference Standards 〈11〉

USP Triclabendazole RS

USP Triclabendazole Related Compound A RS

5-Chloro-6-(2,3-dichlorophenoxy)-2-(methylsulnyl)-1H-benzimidazole.

(C₁₄H₉Cl₃N₂O₂S)        375.65

USP Triclabendazole Related Compound B RS

5-Chloro-6-(2,3-dichlorophenoxy)-1H-benzimidazole-2-thione.

(C₂₃H₇Cl₃N₂OS)         345.62

USP Triclabendazole Related Compound D RS

4-Chloro-5-(2,3-dichlorophenoxy)-2-nitroaniline.

(C₁₂H₇Cl₃N₂O₃ )        333.55 _{(USP 1-Aug-2023)}