Triclosan

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

C₁₂H₇Cl₃O₂ 289.54

Phenol, 5-chloro-2-(2,4-dichlorophenoxy)-;

2,4,4′-Trichloro-2′-hydroxydiphenyl ether CAS RN®: 3380-34-5; UNII: 4NM5039Y5X.

1 DEFINITION

Triclosan contains NLT 97.0% and NMT 103.0% of triclosan (C₁₂H₇Cl₃O₂), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

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 solution, as obtained in the Assay.

3 ASSAY

Change to read:

3.1 Procedure

Standard solution: 0.4 mg/mL of USP Triclosan RS in ethyl acetate

Sample solution: 0.4 mg/mL of Triclosan in ethyl acetate

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: GC
• Detector: Flame ionization
• Column: 0.53-mm × 15-m; coated with a 1.0-µm film of phase G3
• Temperatures
• Injection port: 200°
• Detector: 260°
• Column: See Table 1.

Table 1

• Carrier gas: Helium
• Pressure: 6 psi
• Injection volume: 2 µL

System suitability

• Sample: Standard solution
• Suitability requirements
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of triclosan (C₁₂H₇Cl₃O₂) in the portion of Triclosan taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of triclosan from the Sample solution

rₛ = peak response of triclosan from the Standard solution

Cₛ = concentration of USP Triclosan RS in the Standard solution (mg/mL)

Cᵤ = concentration of Triclosan in the Sample solution (mg/mL)

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

4 IMPURITIES

4.1 Organic Impurities

Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability

• Sample: Standard solution
• Suitability requirements
• Relative standard deviation: NMT 2.0%

Analysis

Sample: Sample solution

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

Result = (r_U/r_T) × 100

r_U = peak response of each impurity in the Sample solution

r_T = sum of all peak responses in the Sample solution

Acceptance criteria

• Individual impurities: NMT 0.1%
• Total impurities: NMT 0.5%

Change to read:

4.2 Limit of 1,3,7-Trichlorodibenzo-p-dioxin, 2,8-Dichlorodibenzo-p-dioxin, 2,8-Dichlorodibenzofuran, and 2,4,8-Trichlorodibenzofuran

Mobile phase: Acetonitrile, water, and glacial acetic acid (70:30:0.1)

Standard solution: Use USP Triclosan Related Compounds Mixture A RS

Sample solution: Transfer 2.0 g of Triclosan into a screw-capped centrifuge tube. Add 5 mL of 2 N potassium hydroxide, and shake for 10 min to dissolve. Add 3 mL of n-hexane, shake for 10 min, and allow the phases to separate. Transfer the organic layer to a suitable container, add another 3 mL of n-hexane to the aqueous layer, shake for 10 min, and allow the phases to separate. Transfer the organic layer to the previous extract, discard the aqueous layer, add 3 mL of 2 N potassium hydroxide to the combined organic layers, shake for 10 min, and allow the phases to separate. Discard the aqueous layer, add another 3 mL of 2 N potassium hydroxide to the combined organic layers, shake for 10 min, and allow the phases to separate. Transfer the organic layer to a suitable container, and evaporate with the aid of a stream of nitrogen to dryness. Dissolve the residue in 1.0 mL of methanol.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 220 nm
• Column: 4.6-mm × 25-cm; 5-μm packing L1
• Flow rate: 1.5 mL/min
• Injection volume: 20 µL

System suitability

• Sample: Standard solution
• Suitability requirements
• Relative standard deviation: NMT 15.0% from the 2,8-dichlorodibenzo-p-dioxin peak

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration of each impurity in the portion of Triclosan taken:

Result = (rᵤ/rₛ) × (Cₛ/W) × V

rᵤ = peak response of each impurity from the Sample solution

rₛ = peak response of the corresponding impurity in USP Triclosan Related Compounds Mixture A RS from the Standard solution

Cₛ = concentration of the corresponding impurity in USP Triclosan Related Compounds Mixture A RS in the Standard solution (µg/mL)

W = weight of Triclosan taken to prepare the Sample solution (g)

V = volume of the Sample solution, 1 mL

Acceptance criteria: See Table 2.

Table 2

Change to read:

Limit of 2,3,7,8-Tetrachlorodibenzo-p-dioxin and 2,3,7,8-Tetrachlorodibenzofuran

[Caution-2,3,7,8-Tetrachlorodibenzo-p-dioxin and 2,3,7,8-tetrachlorodibenzofuran are extremely toxic substances. Exercise all necessary precautions in the conduct of this procedure.]

Stationary phase A: Transfer 10 g of silica gel to a suitable container, add 3 mL of 1 N sodium hydroxide, and mix.

Stationary phase B: Transfer 60 g of silica gel to a suitable container, add 74 mL of concentrated sulfuric acid, and mix.

Chromatographic column A: Transfer 5.1 g of Stationary phase A, 0.5 g of silica gel, 6.2 g of Stationary phase B, and 3.2 g of sodium sulfate to a glass chromatographic column having an internal diameter of 10 mm. Wash the column with 50 mL of n-hexane, and discard the eluate.

Chromatographic column B: Transfer 2.5 g of alumina and 2.5 g of sodium sulfate to a glass chromatographic column having an internal diameter of 6 mm. Wash the column with 30 mL of n-hexane, and discard the eluate.

Internal standard solution: 1.0 pg/µL each of ¹³C-labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin and ¹³C-labeled 2,3,7,8-tetrachlorodibenzofuran prepared as follows. Transfer quantities of ¹³C-labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin and ¹³C-labeled 2,3,7,8-tetrachlorodibenzofuran, in nonane, and dilute if necessary, with 2,2,4-trimethylpentane.

Sample solution: Transfer 30 g of Triclosan into a separatory funnel. Add 30 µL of Internal standard solution, and dissolve in 200 mL of 1 N sodium hydroxide. Extract with four 30-mL portions of n-hexane and combine the extracts. Wash the combined extracts with 20 mL of water, extract the washing with 15 mL of n-hexane, and add the extract to the other combined extracts. Add 3 g of anhydrous sodium sulfate to the combined extracts, allow to stand for 30 min, quantitatively transfer to an appropriate round-bottom flask, and distill, using a distillation apparatus with a Vigreux column, until about 1 mL remains. Transfer this solution to the top of Chromatographic column A, and elute with 50 mL of n-hexane. Collect the eluate on top of Chromatographic column B, and elute with 30 mL of a mixture of n-hexane and methylene chloride (98:2), discarding the eluate. Elute with 40 mL of a mixture of n-hexane and methylene chloride (50:50), collecting the eluates in a round-bottom flask. Distill the combined eluates, using a distillation apparatus with a Vigreux column, until 1 mL remains.

Further concentrate this solution with the aid of a stream of nitrogen to 50 µL, evaporate at room temperature to dryness, and dissolve in 10 µL of 2,2,4-trimethylpentane.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability and Mass Spectrometry 〈736〉.)
• Mode: GC
• Detector: High-resolution mass spectrometer with an electron-impact ionization source
• Column: 0.25-mm × 60-m; coated with a 0.15-µm film of phase G48
• Temperatures
• Injection port: 280°
• Column: See Table 3.

Table 3

• Carrier gas: Helium
• Injection volume: 1 µL

System suitability

• Sample: Internal standard solution
• Suitability requirements
• Signal-to-noise ratio: NLT 50 at a mass-to-charge (m/z) ratio of 321.89

Analysis

Sample: Sample solution

Measure the peak responses at m/z ratios of 319.90, 321.89, 331.88, 333.93, 303.90, 305.90, 315.94, and 317.94.

Acceptance criteria: The peak response for 2,3,7,8-tetrachlorodibenzo-p-dioxin at an m/z ratio of 319.90 is NMT the peak response of the associated internal standard at an m/z ratio of 331.88; the peak response for 2,3,7,8-tetrachlorodibenzofuran at an m/z ratio of 303.90 is NMT the peak response of the associated internal standard at an m/z ratio of 315.94.

Change to read:

4.3 Limit of Monochlorophenols and 2,4-Dichlorophenol

Buffer: Dissolve 1.38 g of sodium phosphate, monobasic, anhydrous and 1.42 g of sodium phosphate, dibasic in 1 L of water.

Mobile phase: Acetonitrile and Buffer (50:50)

Standard solution: 0.5 µg/mL of USP Parachlorophenol RS and 0.1 µg/mL of USP 2,4-Dichlorophenol RS prepared as follows. Dissolve in acetonitrile a suitable amount each of USP Parachlorophenol RS and USP 2,4-Dichlorophenol RS in a suitable volumetric flask, and add an equal volume of water. Dilute appropriately a portion of this solution with a mixture of acetonitrile and water (50:50).

Sample solution: Transfer 250 mg of Triclosan into a 25-mL, low-actinic volumetric flask. Dissolve in 20 mL of acetonitrile, and dilute with water to volume.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: Coulometric electrochemical with electrode 1 set at 0.45 V and electrode 2 set at 0.75 V, both having a positive (oxidative) polarity
• Column: 4.6-mm × 25-cm; 5-μm packing L1
• Flow rate: 1 mL/min
• Injection volume: 20 µL

System suitability

• Sample: Standard solution
• Suitability requirements
• Relative standard deviation: NMT 9.0% for 2,4-dichlorophenol

Analysis

Samples: Standard solution and Sample solution

[Note-The relative retention times for parachlorophenol and 2,4-dichlorophenol are 0.7 and 1.0, respectively.]

Acceptance criteria: The peak responses for parachlorophenol and 2,4-dichlorophenol of the Sample solution are NMT the corresponding peaks of the Standard solution.

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I: NMT 0.1%

Completeness of Solution 〈641〉

Sample: 1.40 g/10 mL of acetone

Acceptance criteria: Meets the requirements

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

Change to read:

USP Reference Standards 〈11〉

USP 2,4-Dichlorophenol RS

2,4-Dichlorophenol.

C₆H₄Cl₂O 163.00

USP Parachlorophenol RS

4-Chlorophenol.

C₆H₅ClO 128.56

USP Triclosan RS

USP Triclosan Related Compounds Mixture A RS

Contains a mixture of the following four compounds:

2,8-Dichlorodibenzofuran.

2,4,8-Trichlorodibenzofuran.

2,8-Dichlorodibenzodioxin.

1,3,7-Trichlorodibenzodioxin.