Propionic Acid

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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^▲C₃H₆O₂           74.08

Propanoic acid;

Propionic acid CAS RN: 79-09-4 _{▲(NF 1-Dec-2022)}

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1 DEFINITION

Propionic Acid contains ^▲NLT 97.0% and NMT 102.0% _{▲(NF 1-Dec-2022)} of propionic acid (C₃H₆O₂ ).

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2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197F

B. CHROMATOGRAPHIC IDENTITY

Analysis: Examine the chromatograms obtained in the Assay.

Acceptance criteria: The retention time of major peak of the Sample solution corresponds to that of the Standard solution._{▲(NF 1-Dec-2022)}

3 ASSAY

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PROCEDURE

^▲Solution A: 10 mM potassium phosphate, monobasic, with the pH adjusted to 2.5 using phosphoric acid

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: 2% (v/v) phosphoric acid in water

System suitability solution: 2.0 mg/mL of USP Propionic Acid RS and 0.008 mg/mL of acrylic acid in Diluent

Standard solution: 2.0 mg/mL of USP Propionic Acid RS in Diluent

Sample solution: 2.0 mg/mL of Propionic Acid in Diluent

Chromatographic system

(See Chromatography (621). System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Column temperature: 45°

Flow rate: 1.0 mL/min

Injection volume: 20 µL

Run time: 35 min

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The approximate relative retention times for related substances are listed in Table 2.]

Suitability requirements

Resolution: NLT 1.5 between the propionic acid peak and the acrylic acid peak, System suitability solution

Tailing factor: NMT 2, determined from the propionic acid peak, Standard solution

Relative standard deviation: NMT 1%, determined from the propionic acid peak, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the Propionic Acid in the portion of sample taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak area of propionic acid from the Sample solution

r_S = peak area of propionic acid from the Standard solution

C_S = concentration of USP Propionic Acid RS in the Standard solution (mg/mL) 

C_U = concentration of Propionic Acid in the Sample solution (mg/mL) 

Acceptance criteria: 97.0%-102.0% _{▲(NF 1-Dec-2022)}

4 IMPURITIES

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4.1 Organic Impurities

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

Sensitivity solution: 0.008 mg/mL of USP Propionic Acid RS in Diluent

Standard solution: 0.016 mg/mL of USP Propionic Acid RS in Diluent

Sample solution: 16 mg/mL of Propionic Acid in Diluent

System suitability

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

[NOTE-The approximate relative retention times for related substances are listed in Table 2.1

Table 2

Suitability requirements

Resolution: NLT 1.5 between the propionic acid peak and the acrylic acid peak, System suitability solution

Relative standard deviation: NMT 5.0%, determined from the propionic acid peak, Standard solution

Signal-to-noise ratio: NLT 10, determined from the propionic acid peak, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity in the portion of sample taken:

                         Result = (r_U/r_S) × (C_S/C_U) × (1/F) x 100

r_U = peak response of each individual impurity from the Sample solution

r_S = peak area of propionic acid from the Standard solution

C_S = concentration of USP Propionic Acid RS in the Standard solution (mg/mL) 

C_U = concentration of Propionic Acid in the Sample solution (mg/mL)

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3.

Table 3

4.2 LIMIT OF NONVOLATILE RESIDUE

Evaporate 20 g of Propionic Acid in a tared dish, and dry at 105° for 1 h: the weight of the residue does not exceed 2.0 mg.

4.3 LIMIT OF ALDEHYDES

Sample solution: Transfer 10.0 mL of Propionic Acid to a glass-stoppered 250-mL conical flask containing 50 mL of water and 10.0 mL of sodium bisulfite solution (1 in 80), insert the stopper, and shake vigorously. Allow the mixture to stand for 30 min.

Blank: Add 50 mL of water and 10.0 mL of sodium bisulfite solution (1 in 80) to a glass-stoppered 250-mL conical flask, insert the stopper, and shake vigorously. Allow the mixture to stand for 30 min.

Titrimetric system

(See Titrimetry (541).)

Mode: Residual titration

Titrant: 0.1 N iodine VS

Endpoint detection: Visual

Analysis: Titrate the Sample solution and the Blank with Titrant to the same brownish-yellow endpoint.

Acceptance criteria: The difference between the volume of 0.1 N iodine required for the Blank and that required for the Sample solution is NMT 1.75 mL.

5 SPECIFIC TESTS

DISTILLING RANGE (721), Method : 138.5°-142.5°

SPECIFIC GRAVITY (841): 0.988-0.993

READILY OXIDIZABLE SUBSTANCES

Sample solution: Dissolve 15 g of sodium hydroxide in 50 mL of water. Cool, add 6 mL of bromine, stirring to effect complete solution, and dilute with water to 2000 mL. Transfer 25.0 mL of this solution to a glass-stoppered 250-mL conical flask containing 100 mL of water, and add 10 mL of sodium acetate solution (1 in 5) and 10.0 mL of Propionic Acid. Allow to stand for 15 min, and add 5 mL of potassium iodide solution (1 in 4) and 10 mL of hydrochloric acid.

Blank: Dissolve 15 g of sodium hydroxide in 50 mL of water. Cool, add 6 mL of bromine, stirring to effect complete solution, and dilute with water to 2000 mL. Transfer 25.0 mL of this solution to a glass-stoppered 250-ml conical flask containing 100 mL of water, and add 10 mL of sodium acetate solution (1 in 5). Allow to stand for 15 min, and add 5 mL of potassium iodide solution (1 in 4) and 10 mL of hydrochloric acid.

Titrimetric system

(See Titrimetry (541).)

Mode: Residual titration

Titrant: 0.1 N sodium thiosulfate VS

Endpoint detection: Visual

Analysis: Titrate the Sample solution and the Blank with Titrant just to the disappearance of the brown color.

Acceptance criteria: The difference between the volume of 0.1 N sodium thiosulfate required for the Blank and that required for the Sample solution is NMT 2.2 mL.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

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^▲ USP REFERENCE STANDARDS (11)

USP Propionic Acid RSA _{▲(NF 1-Dec-2022)}