Triclocarban

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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C₁₃H₉Cl₃N₂O         315.58

Urea, N-(4-chlorophenyl)-N'-(3,4-dichlorophenyl)-; 3,4,4'-Trichlorocarbanilide; 1-(4-Chlorophenyl)-3-(3,4-dichlorophenyl)urea CAS RN: 101-20-2; UNII: BGG1Y1ED0Y. 

1 DEFINITION

Triclocarban contains NLT 97.0% and NMT 103.0% of triclocarban (C₁₂H₂CIN₂O), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

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

PROCEDURE

Mobile phase: Acetonitrile, methanol, water, and glacial acetic acid (400:500:300:1.5)

System suitability solution: 0.1 mg/mL each of USP Triclocarban RS, USP Triclocarban Related Compound A RS, and USP Triclocarban Related Compound C RS in acetonitrile

Standard solution: 0.1 mg/mL of USP Triclocarban RS in acetonitrile. The solution is stable for 12 h.

Sample solution: 0.1 mg/mL of Triclocarban in acetonitrile. The solution is stable for 12 h.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 265 nm

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

Flow rate: 2 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for triclocarban related compound A, triclocarban, and triclocarban related compound C are 0.7, 1.0, and 1.6, respectively.]

Suitability requirements

Resolution: NLT 2.0 between triclocarban related compound A and triclocarban, NLT 2.0 between triclocarban and triclocarban related compound C, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of triclocarban (C₁₃H₉Cl₃N₂O) in the portion of Triclocarban 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 Triclocarban RS in the Standard solution (mg/mL)

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

Acceptance criteria: 97.0%–103.0% on the dried basis

4 IMPURITIES

4.1 ORGANIC IMPURITIES

Mobile phase: Acetonitrile, methanol, water, and glacial acetic acid (370:380:250:1)

Internal standard solution: 0.12 mg/mL of p-nitrochlorobenzene in methanol

Standard solution: 2 µg/mL each of USP Triclocarban RS. USP Triclocarban Related Compound A RS, USP Triclocarban Related Compound C RS, USP Triclocarban Related Compound D Mixture RS, and 2.4 µg/mL of p-nitrochlorobenzene from the Internal standard solution. Dissolve and dilute with methanol to volume.

Sample solution: 0.2 mg/mL of Triclocarban and 2.4 µg/ml. of p-nitrochlorobenzene from the Internal standard solution. Dissolve and dilute with methanol to volume.

Chromatographic system

(See Chromatography (621). System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Column temperature: 40^o

Flow rate: 1.3 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Signal-to-noise ratio: NLT 10 for triclocarban related compound A, triclocarban related compound C, and triclocarban related compound D mixture

Relative standard deviation: NMT 2.0% for triclocarban

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Triclocarban taken:

Result = (R_u /R_s ) × (C_s /C_u ) × 100

R_u = peak response ratio of each impurity to the internal standard from the Sample solution

R_s = peak response ratio of corresponding specied impurity to the internal standard from the Standard solution (use the triclocarban peak response ratio to calculate for any individual impurity)

C_s = concentration of each impurity in the Standard solution (µg/mL)

C_u = concentration of Triclocarban in the Sample solution (µg/mL)

Acceptance criteria: See Table 1.

Table 1

^a Internal standard—for information only.
^b 1,3-Bis(4-chlorophenyl)urea.
^c 1,3-Bis(3,4-dichlorophenyl)urea.
^d Consists of two components, triarylbiuret 1 and triarylbiuret 2. Triarylbiuret 1 is [3,5-bis(4-chlorophenyl)-1-(3,4-dichlorophenyl)biuret] with RRT of 2.72. Triarylbiuret 2 is [1,5-bis(4-chlorophenyl)-3-(3,4-dichlorophenyl)biuret] with RRT of 3.25. The acceptance criteria is the sum of triarylbiuret 1 and triarylbiuret 2.

4.2 CHLOROANILINES

Dimethylformamide solution: 5% dimethylformamide in 1 N hydrochloric acid

Sodium nitrite solution: 2.5 mg/mL of sodium nitrite in water

Ammonium sulfamate solution: 25 mg/mL of ammonium sulfamate in water

N-(1-naphthyl)ethylenediamine dihydrochloride solution: 10 mg/mL in water

Standard stock solution 1: 560 µg/mL of 3,4-dichloroaniline and 440 µg/mL of p-chloroaniline dissolved in 2% of the nal volume with the Dimethylformamide solution. Dilute with 0.2 N hydrochloric acid to volume.

Standard stock solution 2: 56 µg/mL of 3,4-dichloroaniline and 44 µg/mL of p-chloroaniline in 0.2 N hydrochloric acid from Standard stock solution 1

Standard stock solution 3: 5.6 µg/mL of 3,4-dichloroaniline and 4.4 µg/mL of p-chloroaniline in 0.2 N hydrochloric acid from Standard stock solution 2

Standard stock solution 4: 0.56 µg/mL of 3,4-dichloroaniline and 0.44 µg/mL of p-chloroaniline in 0.2 N hydrochloric acid from Standard stock solution 3

Standard solutions: Prepare Standard solutions 1-9 as listed in Table 2. Transfer the aliquot of the Standard stock solution to each individual 25-mL volumetric flask. Place all flasks in an ice bath at 0° to 5 deg for 10 min. Add to each volumetric flask 1 mL of Sodium nitrite solution, shake well, and let the solution stand for 10 min in the ice bath. Add to each flask 1 mL of the Ammonium sulfamate solution, shake well, and allow the reaction to take place for 10 min inside the ice bath. Add 2 mL of the N-(1-naphthyl)ethylenediamine dihydrochloride solution to each Standard solution 1-8, and remove all volumetric flasks from the ice bath. Do not add the N-(1-naphthyl)ethylenediamine dihydrochloride solution to Standard solution 9. Dilute all solutions with 0.2 N hydrochloric acid to volume. Allow to stand for at least 30 s, and measure the absorbance within 15 min.

Table 2

Sample stock solution: Dissolve 500 mg of Triclocarban with 5 mL of the Dimethylformamide solution in a 50-ml beaker, and shake the solution. Continue shaking the solution while adding 15 mL of 0.2 N hydrochloric acid to precipitate the product, and shake for 15 min. Filter the suspension into a 50-mL volumetric flask, and dilute with 0.2 N hydrochloric acid to volume.

Sample solution: Transfer 10 mL of the Sample stock solution to a 25-mL volumetric flask, and place in an ice bath at 0 deg to 5 deg | for 10 min. Add 1 mL of the Sodium nitrite solution, shake well, and let the solution stand for 10 min in the ice bath. Add 1 mL of the Ammonium sulfamate solution, shake well, and allow to stand for 10 min. Add 1 mL of the N-(1-naphthyl) ethylenediamine dihydrochloride solution, and remove the solution from the ice bath. Dilute with 0.2 N hydrochloric acid to volume. Allow to stand for at least 30 s, and measure the absorbance within 15 min.

Sample solution blank: Follow the procedure described in the preparation of the Sample solution but do not add the N-(1-naphthyl)ethylenediamine dihydrochloride solution.

Instrumental conditions

Mode: UV

Analytical wavelength: 552 nm

Analysis

Samples: Standard solutions and Sample solution

Calibrate the absorbance to zero with Standard solution 9. Generate a calibration curve of absorbance against concentration of total chloroaniline using the data from Standard solutions 1-8. Determine the concentration, C_s , in µg/mL of chloroanilines in the Sample solution using the calibration curve. Calculate the concentration, in ppm, of chloroanilines in the portion of Triclocarban taken:

Result = (C_s /C_u ) × F

C_s = concentration of chloroanilines in the Sample solution (µg/mL)

C_u = concentration of Triclocarban in the Sample solution (µg/mL)

F = conversion factor to ppm (106)

Acceptance criteria: NMT 400 ppm

5 SPECIFIC TESTS

 Loss on Drying 〈731〉

Sample: Dry a sample at 110° for 4 h.

Acceptance criteria: NMT 0.2%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed container. Store at ambient temperature and humidity.

USP Reference Standards 〈11〉

USP Triclocarban RS

USP Triclocarban Related Compound A RS

1,3-Bis(4-chlorophenyl)urea.

C₁₃H₁₀Cl₂N₂O       281.14

USP Triclocarban Related Compound C RS

1,3-Bis(3,4-dichlorophenyl)urea.

C₁₃H₈Cl₄N₂O         350.03

USP Triclocarban Related Compound D Mixture RS

Mixture of triarylbiuret 1 (3,5-bis(4-chlorophenyl)-1-(3,4-dichlorophenyl)biuret and triarylbiuret 2 (1,5-bis(4-chlorophenyl)-3-(3,4-dichlorophenyl)biuret).

C₂₀H₁₃Cl₄N₃O₂       469.15