Propylene Glycol

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

Propylene Glycol contains NLT 99.5% of C₃H₈O₂.

2 IDENTIFICATION

[Note—Compliance is determined by meeting the requirements of Identification tests A, B, and C.]

Change to read:

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

[Note—Undried specimen.]

B. Limit of Diethylene Glycol and Ethylene Glycol

Diluent: Methanol

Standard solution: 2.0 mg/mL of USP Propylene Glycol RS, 0.050 mg/mL of USP Ethylene Glycol RS, 0.050 mg/mL of USP Diethylene Glycol RS, and 0.10 mg/mL of 2,2,2-trichloroethanol (internal standard) in methanol

Sample solution: 50 mg/mL of Propylene Glycol and 0.10 mg/mL of 2,2,2-trichloroethanol (internal standard) in methanol

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.53-mm × 30-m fused-silica coated with 3.0-µm G43 stationary phase, and a deactivated split liner with glass wool

Temperature

Injector: 220°

Detector: 250°

Column: See the temperature program table below.

Carrier gas: Helium

Injection size: 1.0 µL

Flow rate: 4.5 mL/min

Injection type: The split flow ratio is about 10:1.

System suitability

Sample: Standard solution

[Note—For informational purposes only. See Impurity Table 1 for relative retention times for ethylene glycol, internal standard, and diethylene glycol. The retention time for propylene glycol is 4 min.]

Impurity Table 1

Suitability requirements

Resolution: NLT 5 between ethylene glycol and propylene glycol

Analysis

Sample: Sample solution

Acceptance criteria

Diethylene glycol: If a peak at the retention time for diethylene glycol is present in the Sample solution, the peak response ratio relative to 2,2,2-trichloroethanol is NMT the peak response ratio for diethylene glycol relative to 2,2,2-trichloroethanol in the Standard solution: NMT 0.10% for diethylene glycol.

Ethylene glycol: If a peak at the retention time for ethylene glycol is present in the Sample solution, the peak response ratio relative to 2,2,2-trichloroethanol is not more than the peak response ratio for ethylene glycol relative to 2,2,2-trichloroethanol in the Standard solution: NMT 0.10% for ethylene glycol is found.

C. Examine the chromatograms obtained in Identification test B. The retention time of the propylene glycol peak of the Sample solution corresponds to that of the Standard solution.

3 ASSAY

Procedure

Sample: Propylene Glycol

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC

Detector: Thermal conductivity

Column: 1-m × 4-mm; 5% phase G16; support S5

Temperature

Injector: 240°

Detector: 250°

Column: Increase from 120° to 200° at a rate of 5°/min

Carrier gas: Helium

Injection size: 10 µL

[Note—The approximate retention time for propylene glycol is 5.7 min, and the approximate retention times for the three isomers of dipropylene glycol, when present, are 8.2, 9.0, and 10.2 min, respectively.]

Analysis: Calculate the percentage of C₃H₈O₂ in the Sample by dividing the area under the propylene glycol peak by the sum of the areas under all of the peaks, excluding those due to air and water, and multiplying by 100:

Result = [ r / ( r + Σr ) ] × 100

r = peak response for Propylene Glycol from the Sample

Σr = sum of individual impurity peak responses, excluding those due to air and water, from the Sample

Acceptance criteria: NLT 99.5%

4 IMPURITIES

Inorganic Impurities

Residue on Ignition 〈281〉

Sample: 50 g

Analysis: Heat the Sample in a tared 100-mL shallow dish until it ignites, and allow it to burn without further application of heat in a place free from drafts. Cool, moisten the residue with 0.5 mL of sulfuric acid, and ignite to constant weight.

Acceptance criteria: The weight of the residue is NMT 3.5 mg.

Chloride and Sulfate, Chloride 〈221〉: A 1-mL portion shows no more chloride than corresponds to 0.10 mL of 0.020 N hydrochloric acid (70 ppm).

Chloride and Sulfate, Sulfate 〈221〉: A 5.0-mL portion shows no more sulfate than corresponds to 0.30 mL of 0.020 N sulfuric acid (60 ppm).

5 SPECIFIC TESTS

Specific Gravity 〈841〉: 1.035–1.037

 Acidity

Sample: 10 mL of Propylene Glycol

Analysis: Add 1 mL of phenolphthalein TS to 50 mL of water, then add 0.1 N sodium hydroxide until the solution remains pink for 30 s. Add the Sample, and titrate with 0.10 N sodium hydroxide until the original pink color returns and remains for 30 s.

Acceptance criteria: NMT 0.20 mL of 0.10 N sodium hydroxide

Water Determination, Method I 〈921〉: NMT 0.2%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Diethylene Glycol RS

USP Ethylene Glycol RS

USP Propylene Glycol RS