Thimerosal Topical Solution

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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1 DEFINITION

Thimerosal Topical Solution contains, in each 100 mL, NLT 95 mg and NMT 105 mg of thimerosal.

[Note—Thimerosal Topical Solution is sensitive to some metals.]

2 IDENTIFICATION

A.

Sample: 50 mL of Topical Solution

Analysis 1: Pass hydrogen sulfide through the Sample.

Acceptance criteria 1: No black discoloration or black precipitate is formed.

Analysis 2: Add 3 or 4 drops of bromine to the Sample, mix, and warm on a steam bath to expel the excess bromine. Add 5 mL of 3 N hydrochloric acid, filter, and pass hydrogen sulfide through the filtrate.

Acceptance criteria 2: A black precipitate is formed.

B.

Sample: 1 mL of Topical Solution

Analysis: To the Sample add 9 mL of water, mix, and add 1 mL of cupric sulfate TS.

Acceptance criteria: A green color is produced immediately and is followed by the gradual precipitation of flocculent, greenish brown particles.

3 ASSAY

Procedure

The Standard solutions and Sample solution may be diluted with water, if necessary, to yield solutions of suitable concentration, adaptable to the linear or working range of the instrument.

Solution A: Dissolve 50 g of stannous chloride in 100 mL of hydrochloric acid on a steam bath, cool, and dilute with water to 500 mL. Use within 3 months.

Standard stock solution A: 1.8 μg/mL of USP Thimerosal RS

Standard stock solution B: 2.0 μg/mL of USP Thimerosal RS

Standard stock solution C: 2.2 μg/mL of USP Thimerosal RS

Standard solution A: Pipet 20 mL of Standard stock solution A into a 100-mL volumetric flask. Add 5 mL of sulfuric acid, cool, add 3 mL of nitric acid, and mix. Add potassium permanganate crystals, while mixing, until the purple color persists for NLT 15 min. Add 200 mg of potassium persulfate, mix, and heat on a steam bath for 2 h. Cool, and dilute with water to volume.

Standard solution B: Pipet 20 mL of Standard stock solution B into a 100-mL volumetric flask. Add 5 mL of sulfuric acid, cool, add 3 mL of nitric acid, and mix. Add potassium permanganate crystals, while mixing, until the purple color persists for NLT 15 min. Add 200 mg of potassium persulfate, mix, and heat on a steam bath for 2 h. Cool, and dilute with water to volume.

Standard solution C: Pipet 20 mL of Standard stock solution C into a 100-mL volumetric flask. Add 5 mL of sulfuric acid, cool, add 3 mL of nitric acid, and mix. Add potassium permanganate crystals, while mixing, until the purple color persists for NLT 15 min. Add 200 mg of potassium persulfate, mix, and heat on a steam bath for 2 h. Cool, and dilute with water to volume.

Sample stock solution: Pipet 2 mL of Topical Solution into a 1000-mL volumetric flask, and dilute with water to volume.

Sample solution: Pipet 20 mL of Sample stock solution into a 100-mL volumetric flask. Add 5 mL of sulfuric acid, cool, add 3 mL of nitric acid, and mix. Add potassium permanganate crystals, while mixing, until the purple color persists for NLT 15 min. Add 200 mg of potassium persulfate, mix, and heat on a steam bath for 2 h. Cool, and dilute with water to volume.

Instrumental conditions

Mode: Flameless atomic absorption spectroscopy

Lamp: Mercury hollow-cathode

Blank solution: Pipet 20 mL of water into a 100-mL volumetric flask. Add 5 mL of sulfuric acid, cool, add 3 mL of nitric acid, and mix. Add potassium permanganate crystals, while mixing, until the purple color persists for NLT 15 min. Add 200 mg of potassium persulfate, mix, and heat on a steam bath for 2 h. Cool, and dilute with water to volume.

Analysis

Samples: Standard solutions A, B, and C, Sample solution, and Blank solution

Proceed with each of the Samples as follows. Pipet 3 mL into the scrubbing chamber of a suitable system designed for determination of mercury. Dilute with water to 150 mL, and add hydroxylamine hydrochloride solution (1 in 10) to reduce the excess permanganate. Add 5 mL of Solution A, and immediately attach the scrubbing chamber to the system. Concomitantly determine the absorbance of each solution at an integration time of 15 s. Use the absorbance of the Blank solution to correct the absorbances of Standard solutions A, B, and C, and the Sample solution. Plot the corrected absorbances of the standards versus their respective concentrations of the Standard stock solutions, in μg/mL, and from the curve so obtained, determine the concentration, C, in μg/mL, of the Sample solution.

Calculate the quantity, in mg, of thimerosal in each 100 mL of Topical Solution taken:

Result = C × D × V × F

C = measured concentration of the Sample solution (μg/mL)

D = dilution of the Sample stock solution, 500

V = volume of Topical Solution, 100 mL

F = unit conversion, 1 mg/1000 μg

Acceptance criteria: 95–105 mg

4 SPECIFIC TESTS

pH 〈791〉: 9.6–10.2

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers, and avoid exposure to excessive heat.

USP Reference Standards 〈11〉

USP Thimerosal RS