Ethyl Acetate

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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C₄H₈O₂   88.11 

Acetic acid, ethyl ester; 

Ethyl acetate CAS RN®: 141-78-6. 

1 DEFINITION 

Ethyl Acetate contains NLT 98.0% and NMT 102.0% of ethyl acetate (C₄H₈O₂).

2 IDENTIFICATION 

Change to read:

Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197F 

3 ASSAY 

Procedure 

Diluent: N,N-dimethylacetamide 

System suitability solution: 2.0 mg/mL of USP Ethyl Acetate RS and 20 µg/mL of USP Methyl Ethyl Ketone RS in Diluent Standard solution: 2.0 mg/mL of USP Ethyl Acetate RS in Diluent 

Sample solution: 2.0 mg/mL of Ethyl Acetate in Diluent 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: GC 

Detector: Flame ionization 

Column: 0.32-mm × 60-m; coated with a 1.8-µm lm of phase G43 

Temperatures 

Detector: 250° 

Injection port: 210° 

Column: See Table 1. 

Table 1 

Carrier gas: Helium 

Flow rate: 3.0 mL/min 

Injection volume: 1 µL 

Injection type: Split injection, split ratio 30:1 

Run time: 30.3 min 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—The relative retention times for methyl ethyl ketone and ethyl acetate are 0.97 and 1.0, respectively.] Suitability requirements 

Resolution: NLT 2.0 between the methyl ethyl ketone and ethyl acetate peaks, System suitability solution 

Tailing factor: NMT 1.5 for the ethyl acetate peak, Standard solution 

Relative standard deviation: NMT 2.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of ethyl acetate (C₄H₈O₂) in the portion of Ethyl Acetate taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak area of ethyl acetate from the Sample solution

r_S = peak area of ethyl acetate from the Standard solution

C_S = concentration of USP area of ethyl acetate RS in the Standard solution (mg/mL)

C_U = concentration of area of ethyl acetate in the Sample solution (mg/mL)

P = labeled purity of USP Ethyl Acetate RS 

Acceptance criteria: 98.0%–102.0% 

4 IMPURITIES 

Limit of Nonvolatile Residue 

Sample: Ethyl Acetate 

Analysis: Evaporate the Sample in a tared porcelain dish on a steam bath, and dry at 105° for 1 h. Acceptance criteria: NMT 0.02% 

Change to read: 

Chromatographic Purity 

Diluent and Chromatographic system: Proceed as directed in the Assay. 

System suitability solution: 0.16 mg/mL each of acetaldehyde and methanol, 160 mg/mL of Ethyl Acetate, and 1.6 mg/mL of USP Methyl Ethyl Ketone RS in Diluent 

Sensitivity solution: 0.08 mg/mL each of acetaldehyde, USP Ethyl Acetate RS, and USP 1-Ethoxy-2-methylpropane RS in Diluent Methyl compounds identication solution: 0.16 mg/mL each of methanol, methyl acetate, and methyl isobutyrate in Diluent Standard solution: 0.16 mg/mL each of acetaldehyde, USP Ethyl Acetate RS, and USP 1-Ethoxy-2-methylpropane RS in Diluent Sample solution: 160 mg/mL of Ethyl Acetate in Diluent 

System suitability 

Samples: System suitability solution, Sensitivity solution, and Standard solution 

[Note—The relative retention times for acetaldehyde, methanol, methyl ethyl ketone, ethyl acetate, and 1-ethoxy-2-methylpropane are 0.29, 0.31, 0.97, 1.0, and 1.1, respectively.] 

Suitability requirements 

Resolution: NLT 2.0 between the acetaldehyde and methanol peaks; NLT 2.0 between the methyl ethyl ketone and ethyl acetate peaks, System suitability solution 

Signal-to-noise ratio: NLT 20 for the acetaldehyde, ethyl acetate, and 1-ethoxy-2-methylpropane peaks, Sensitivity solution Tailing factor: NMT 1.5 for the acetaldehyde, ethyl acetate, and 1-ethoxy-2-methylpropane peaks, Standard solution Relative standard deviation: NMT 5.0% for acetaldehyde, ethyl acetate, and 1-ethoxy-2-methylpropane, Standard solution Analysis 

Samples: Methyl compounds identification solution, Standard solution, and Sample solution 

Calculate the percentage of acetaldehyde and 1-ethoxy-2-methylpropane in the portion of Ethyl Acetate taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak area of acetaldehyde or 1-ethoxy-2-methylpropane from the Sample solution

r_S = peak area of acetaldehyde or 1-ethoxy-2-methylpropane from the Standard solution

C_S = concentration of acetaldehyde or USP 1-Ethoxy-2-methylpropane RS in the Standard solution (mg/mL)

C_U = concentration of area of ethyl acetate in the Sample solution (mg/mL)

Identify the methanol, methyl acetate, and methyl isobutyrate peaks in the Sample solution based on those in the Methyl compounds identification solution. 

Calculate the content of methyl compounds in the portion of Ethyl Acetate taken: 

Result = (r_T/r_S) × F 

r_T = sum of the peak areas of methanol, methyl acetate, and methyl isobutyrate from the Sample solution 

r_S = peak area of ethyl acetate from the Standard solution 

F = limit of methyl compounds, in percentage, 0.1 

Acceptance criteria 

Acetaldehyde: NMT 0.1% 

1-Ethoxy-2-methylpropane: NMT 0.1% 

Methyl compounds: NMT 0.1% 

Other impurities: NMT 0.3%; the sum of all other peaks areas in the chromatogram of the Sample solution, excluding the ethyl acetate, specified impurities, and solvent peaks areas, is not greater than three times the ethyl acetate peak area of the Standard solution. 

5 SPECIFIC TESTS 

Acidity 

Sample solution: 2.0 mL of Ethyl Acetate in 10 mL of neutralized alcohol 

Analysis: Add 2 drops of phenolphthalein TS to the Sample solution. Neutralize with 0.10 N sodium hydroxide. 

Acceptance criteria: NMT 0.10 mL of 0.10 N sodium hydroxide is required. 

Readily Carbonizable Substances Test 〈271〉 

Sample: 2 mL of Ethyl Acetate 

Analysis: Add the Sample carefully to 10 mL of sulfuric acid to form separate layers. 

Acceptance criteria: No dark zone is developed within 15 min. 

Specific Gravity 〈841〉: 0.894–0.898 

Bacterial Endotoxins Test 〈85〉: If labeled for use in preparing parenteral dosage forms, it also meets the following requirements. The level of bacterial endotoxins is such that the requirement in the relevant dosage form monographs(s) in which Ethyl Acetate is used can be met. Where the label states that Ethyl Acetate must be subjected to further processing during the preparation of injectable dosage forms, the level of bacterial endotoxins is such that the requirement in the relevant dosage form monograph(s) in which Ethyl Acetate is used can be met. 

6 ADDITIONAL REQUIREMENTS 

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

Labeling: Where Ethyl Acetate is intended for use in the manufacture of injectable dosage forms, it is so labeled. Where Ethyl Acetate must be subjected to further processing during the preparation of injectable dosage forms to ensure acceptable levels of bacterial endotoxins, it is so labeled. 

USP Reference Standards 〈11〉 

USP Ethyl Acetate RS 

USP 1-Ethoxy-2-methylpropane RS 

USP Methyl Ethyl Ketone RS