Ethylparaben Sodium

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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C₉H₉NaO₃  188.2

Benzoic acid, 4-hydroxy-, methyl ester, sodium salt;

Ethyl p-hydroxybenzoate, sodium salt;

Sodium 4-ethoxycarbonylphenolate CAS RN^®: 35285-68-8.

1 DEFINITION

Ethylparaben Sodium contains NLT 95.0% and NMT 102.0% of ethylparaben sodium (C₉H₉NaO₃), calculated on the anhydrous basis.

2 IDENTIFICATION

2.1 A.

Standard: 0.5 g of USP Ethylparaben RS

Sample: 0.5 g of Ethylparaben Sodium

Analysis: Dissolve the Sample in 5 mL of water, acidify with hydrochloric acid, and filter the resulting precipitate. Wash the precipitate with water, and dry under vacuum at 80° for 2 h.

Acceptance criteria: The IR absorption spectrum of a Mineral oil dispersion of the Sample exhibits maxima only at the same wavelengths as those of a similar preparation of the Standard.

2.2 B.

Sample solution: Ignite 0.3 g of Ethylparaben Sodium, cool, and dissolve the residue in about 3 mL of 3 N hydrochloric acid.

Acceptance criteria: A platinum wire dipped in the Sample solution imparts an intense, persistent yellow color to a nonluminous flame.

3 ASSAY

3.1 PROCEDURE

Mobile phase: Methanol and a 6.8-g/L solution of potassium dihydrogen phosphate (65:35)

System suitability solution: 5.0 µg/mL each of p-hydroxybenzoic acid, USP Methylparaben RS, and USP Ethylparaben RS in Mobile phase

Standard solution: Dissolve 50.0 mg of USP Ethylparaben RS in 2.5 mL of methanol, and dilute with Mobile phase to 50.0 mL. Dilute 10.0 mL of this solution with Mobile phase to 100.0 mL.

Sample solution: Dissolve 50.0 mg of Ethylparaben Sodium in 2.5 mL of methanol, and dilute with Mobile phase to 50.0 mL. Dilute 10.0 mL of

this solution with Mobile phase to 100.0 mL.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 272 nm

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

Flow rate: 1.3 mL/min

Injection volume: 10 µL

Run time: About 4 times the retention time of the ethylparaben peak

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The retention time of ethylparaben is about 2.9 min; the relative retention times for p-hydroxybenzoic acid, methylparaben, and ethylparaben are about 0.5, 0.8, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between methylparaben and ethylparaben peaks, System suitability solution

Relative standard deviation: NMT 0.85% for six injections, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ethylparaben sodium in the portion of Ethylparaben Sodium taken:

Result = (r_U/r_S) x (C_S/C_U) x (M_r1/M_r2) x P

r_U = peak area of ethylparaben from the Sample solution

r_S = peak area of ethylparaben from the Standard solution

C_S = concentration of USP Ethylparaben RS in the Standard solution

C_U = concentration of Ethylparaben Sodium in the Sample solution

M_r1 = molecular weight of ethylparaben sodium, 188.2

M_r2 = molecular weight of ethylparaben, 166.17

P = labeled purity of USP Ethylparaben RS expressed as a percentage

Acceptance criteria: 95.0%-102.0% on the anhydrous basis

4 IMPURITIES

4.1 RELATED COMPOUNDS

Mobile phase, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: Dilute 1.0 mL of the Sample solution with Mobile phase to 20.0 mL. Dilute 1.0 mL of this solution with Mobile phase to 10.0 mL.

System suitability

Sample: System suitability solution

[NOTE-The retention time of ethylparaben is about 2.9 min; the relative retention times for p-hydroxybenzoic acid, methylparaben, and ethylparaben are about 0.5, 0.8, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between methylparaben and ethylparaben peaks

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria

p-Hydroxybenzoic acid: The peak area in the Sample solution, multiplied by 1.4 to correct for the calculation of content, is NMT 6 times the area of the principal peak in the Standard solution; NMT 3.0%.

Unspecified impurities: The peak area of each impurity in the Sample solution is NMT the area of the principal peak in the Standard solution; NMT 0.5%.

Total impurities: The total peak area for all unspecified impurities in the Sample solution is NMT twice the area of the principal peak in the

Standard solution; NMT 1.0%.

4.2 CHLORIDE AND SULFATE, Chloride (221)

Sample: 0.2 g

Control solution: 0.10 mL of 0.020 N hydrochloric acid

Acceptance criteria: 0.035%; the Sample shows no more chloride than the Control solution.

4.3 CHLORIDE AND SULFATE, Chloride (221)

Sample: 0.2 g

Control solution: 0.10 mL of 0.020 N hydrochloric acid

Acceptance criteria: 0.035%; the Sample shows no more chloride than the Control solution.

4.4 CHLORIDE AND SULFATE, Sulfate (221)

Sample: 1.0 g

Control solution: 0.31 mL of 0.020 N sulfuric acid

Acceptance criteria: 0.030%; the Sample shows no more sulfate than the Control solution.

5 SPECIFIC TESTS

PH (791)

Sample solution: 1 mg/mL

Acceptance criteria: 9.5-10.5

WATER DETERMINATION, Method (921): NMT 5.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

USP REFERENCE STANDARDS (11)

USP Ethylparaben RS

USP Methylparaben RS