Hexachlorophene

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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C₁₃H₆Cl₆O₂ 406.90

Phenol, 2,2′-methylenebis[3,4,6-trichloro]-;

2,2′-Methylenebis[3,4,6-trichlorophenol] CAS RN®: 70-30-4; UNII: IWW5FV6NK2.

1 DEFINITION

Hexachlorophene contains NLT 98.0% and NMT 100.5% of hexachlorophene (C₁₃H₆Cl₆O₂), calculated on the dried basis. 

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

B.

Sample solution: 5 mg of Hexachlorophene in 5 mL of alcohol

Analysis: To the Sample solution add 1 drop of ferric chloride TS.

Acceptance criteria: A transient purple color is produced immediately.

3 ASSAY

Procedure

Sample: 1.5 g of Hexachlorophene

Analysis: Dissolve the Sample in 25 mL of alcohol, and titrate with 0.1 N sodium hydroxide VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N sodium hydroxide is equivalent to 40.69 mg of hexachlorophene (C₁₃H₆Cl₆O₂).

Acceptance criteria: 98.0%–100.5% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

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

[Caution—Because 2,3,7,8-tetrachlorodibenzo-p-dioxin is an extremely toxic substance, exercise all necessary precautions in the conduct of this procedure.]

Standard solution: 0.01 µg/mL of 2,3,7,8- tetrachlorodibenzo-p-dioxin1

Sample solution: Dissolve 10.0 g of Hexachlorophene in 50 mL of methanol, transfer to a 1-L separator with the aid of 25 mL of methanol, add 25 mL of 2.5 N lithium hydroxide and 225 mL of water, and extract with two 200-mL portions of freshly distilled n-hexane. Dry the combined n-hexane extracts over anhydrous sodium sulfate, filter, and evaporate on a rotary evaporator at a bath temperature not exceeding 40° to a volume of 15 mL. Transfer this solution in portions to a 12-mL centrifuge tube, concentrating each time in a gentle stream of nitrogen in a warm water bath to a volume of 1 mL. Rinse the flask with 15 mL of n-hexane, and evaporate similarly. Wash down the walls of the tube with 10 mL of n-hexane, and again evaporate to a volume of 1.0 mL.

Cool, and transfer to a microcolumn that has been prepared in the following manner. Place a small plug of glass wool in a 5-mm × 15-mm pipet, add a small quantity of sand and 1.0 g of basic alumina, tap several times to pack down the alumina, and heat in a vacuum oven at 110° for 3 h. Store under vacuum.

Elute the column with 10 mL of a mixture of n-hexane and methylene chloride (9:1), using a portion to rinse the tube. Collect the eluate in a 12-mL graduated centrifuge tube, and concentrate in a gentle stream of nitrogen in a warm water bath to a volume of 1.0 mL.

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC-MS (see Mass Spectrometry 〈736〉)

Detector: Multiple-ion

Column: 2-mm × 1-m glass; liquid phase G1 on support S1

Temperatures

Column: 250°

Injection port: 300°

Carrier gas: Helium

Flow rate: 40 mL/min

Injection volume: 2.0 µL

4.2 Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: NMT 1 ppb; the sum of the peak heights at mass values of 320, 322, and 324 of the Sample solution is not greater than the sum of the peak heights at the same mass values of the Standard solution.

5 SPECIFIC TESTS

Melting Range or Temperature 〈741〉: 161°–167°

Loss on Drying 〈731〉

Analysis: Dry a sample at 105° for 4 h. Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Hexachlorophene RS

1 A solution in anisole is available commercially from KOR Isotopes, Div. of ECO, Inc., 56 Rogers St., Cambridge, MA 02142. This solution may be diluted with a mixture of n-hexane and methylene chloride (9:1) to the required concentration.