Glycerin
C3H8O3 92.10
1,2,3-Propanetriol;
Glycerol
[56-81-5].
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C3H8O3 92.10
1,2,3-Propanetriol;
Glycerol
[56-81-5].DEFINITION
Glycerin contains NLT 99.0% and NMT 101.0% of C3H8O3, calculated on the anhydrous basis.
IDENTIFICATION
[Note—Compliance is determined by meeting the requirements for Identification tests A, B, and C. ]
• B. Limit of Diethylene Glycol and Ethylene Glycol
Standard solution:
2.0 mg/mL of USP Glycerin 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 Glycerin and 0.10 mg/mL of 2,2,2-trichloroethanol (internal standard) in methanol
Chromatographic system
Mode:
GC
Detector:
Flame ionization
Column:
0.53-mm × 30-m fused-silica analytical column 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.
| Initial Temperature ( ) |
Temperature Ramp ( /min) |
Final Temperature ( ) |
Hold Time at Final Temperature (min) |
|---|---|---|---|
| 100 | — | 100 | 4 |
| 100 | 50 | 120 | 10 |
| 120 | 50 | 220 | 6 |
Carrier gas:
Helium
Injection size:
1.0 µL
Flow rate:
4.5 mL/min
Injection type:
Split ratio, about 10:1
System suitability
Sample:
Standard solution
[Note—The relative retention times for ethylene glycol, 2,2,2-trichloroethanol, diethylene glycol, and glycerin are about 0.3, 0.6, 0.8 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 1.5 between diethylene glycol and glycerin
Analysis
Sample:
Sample solution
Acceptance criteria:
If a peak at the retention times for the diethylene glycol or ethylene 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 or ethylene glycol relative to 2,2,2-trichloroethanol in the Standard solution; NMT 0.10% each for diethylene glycol and ethylene glycol is found.
• C.
Examine the chromatograms obtained in Identification test B. The retention time of the glycerin peak of the Sample solution corresponds to that obtained in the Standard solution.
ASSAY
• Procedure
Sodium periodate solution:
Dissolve 60 g of sodium metaperiodate in sufficient water containing 120 mL of 0.1 N sulfuric acid to make 1000 mL. Do not heat to dissolve the periodate. If the solution is not clear, pass through a sintered-glass filter. Store the solution in a glass-stoppered, light-resistant container. Test the suitability of this solution as follows. Pipet 10 mL into a 250-mL volumetric flask, and dilute with water to volume. To 550 mg of Glycerin dissolved in 50 mL of water, add 50 mL of the diluted periodate solution with a pipet. For a blank, pipet 50 mL of the solution into a flask containing 50 mL of water. Allow the solutions to stand for 30 min, then to each add 5 mL of hydrochloric acid and 10 mL of potassium iodide TS, and rotate to mix. Allow to stand for 5 min, add 100 mL of water, and titrate with 0.1 N sodium thiosulfate, shaking continuously and adding 3 mL of starch TS as the endpoint is approached. The ratio of the volume of 0.1 N sodium thiosulfate required for the glycerin–periodate mixture to that required for the blank should be between 0.750 and 0.765.
Analysis:
Transfer 400 mg of Glycerin to a 600-mL beaker, dilute with 50 mL of water, add bromothymol blue TS, and acidify with 0.2 N sulfuric acid to a definite green or greenish yellow color. Neutralize with 0.05 N sodium hydroxide to a definite blue endpoint, free from green color. Prepare a blank containing 50 mL of water, and neutralize in the same manner. Pipet 50 mL of the Sodium periodate solution into each beaker, mix by swirling gently, cover with a watch glass, and allow to stand for 30 min at room temperature (not exceeding 35) in the dark or in subdued light. Add 10 mL of a mixture of equal volumes of ethylene glycol and water, and allow to stand for 20 min. Dilute each solution with water to 300 mL, and titrate with 0.1 N sodium hydroxide VS to a pH of 8.1 ± 0.1 for the specimen under assay and 6.5 ± 0.1 for the blank, using a pH meter. Each mL of 0.1 N sodium hydroxide, after correction for the blank, is equivalent to 9.210 mg of C3H8O3.
) in the dark or in subdued light. Add 10 mL of a mixture of equal volumes of ethylene glycol and water, and allow to stand for 20 min. Dilute each solution with water to 300 mL, and titrate with 0.1 N sodium hydroxide VS to a pH of 8.1 ± 0.1 for the specimen under assay and 6.5 ± 0.1 for the blank, using a pH meter. Each mL of 0.1 N sodium hydroxide, after correction for the blank, is equivalent to 9.210 mg of C3H8O3.
Acceptance criteria:
99.0%–101.0% on the anhydrous basis
IMPURITIES
Inorganic Impurities
• Chloride and Sulfate, Chloride 
221
:
A 7.0-g portion shows no more chloride than corresponds to 0.10 mL of 0.020 N hydrochloric acid (NMT 10 ppm).
221:
A 7.0-g portion shows no more chloride than corresponds to 0.10 mL of 0.020 N hydrochloric acid (NMT 10 ppm).
• Chloride and Sulfate, Sulfate 221:
A 10-g portion shows no more sulfate than corresponds to 0.20 mL of 0.020 N sulfuric acid (NMT 20 ppm).
221:
A 10-g portion shows no more sulfate than corresponds to 0.20 mL of 0.020 N sulfuric acid (NMT 20 ppm).
• Heavy Metals 231
231
Analysis:
Mix 4.0 g with 2 mL of 0.1 N hydrochloric acid, and dilute with water to 25 mL.
Acceptance criteria:
NMT 5 ppm
• Residue on Ignition 281:
Heat 50 g in an open, shallow 100-mL porcelain 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: the weight of the residue does not exceed 5 mg (0.01%).
281:
Heat 50 g in an open, shallow 100-mL porcelain 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: the weight of the residue does not exceed 5 mg (0.01%).
Organic Impurities
• Procedure 1: Related Compounds
System suitability solution:
0.5 mg/mL each of USP Diethylene Glycol RS and USP Glycerin RS
Sample solution:
50 mg/mL of Glycerin
Chromatographic system
Mode:
GC
Detector:
Flame ionization
Column:
0.53-mm × 30-m fused-silica analytical column coated with 3.0-µm G43 stationary phase, and an inlet liner having an inverted cup or spiral structure
Temperature
Injector:
220
Detector:
250
Column:
See the temperature program table below.
| Initial Temperature ( ) |
Temperature Ramp ( /min) |
Final Temperature ( ) |
Hold Time at Final Temperature (min) |
|---|---|---|---|
| 100 | — | 100 | — |
| 100 | 7.5 | 220 | 4 |
Carrier gas:
Helium
Injection size:
0.5 µL
Linear velocity:
38 cm/s
Injection type:
Split ratio, about 10:1
System suitability
Sample:
System suitability solution
Suitability requirements
Resolution:
NLT 7.0 between diethylene glycol and glycerin
Analysis
Sample:
Sample solution
Calculate the percentage of each impurity, excluding any solvent peaks and diethylene glycol, in the portion of Glycerin taken:
Result = (rU/rT) × 100
| rU | = | = peak response of each individual impurity from the Sample solution |
| rT | = | = sum of the responses of all the peaks from the Sample solution |
Acceptance criteria
Individual impurities:
NMT 0.1%
Total impurities:
NMT 1.0%
• Procedure 2: Limit of Chlorinated Compounds
Sample:
5 g of Glycerin
Analysis:
Transfer the Sample into a dry, round-bottom, 100-mL flask. Add 15 mL of morpholine, and connect the flask by a ground joint to a reflux condenser. Reflux gently for 3 h. Rinse the condenser with 10 mL of water, receiving the washings in the flask, and cautiously acidify with nitric acid. Transfer the solution to a suitable comparison tube, add 0.50 mL of silver nitrate TS, and dilute with water to 50.0 mL.
Acceptance criteria:
The turbidity is not greater than that of a blank to which 0.20 mL of 0.020 N hydrochloric acid has been added, the refluxing being omitted (NMT 30 ppm of Cl).
• Procedure 3: Fatty Acids and Esters
Sample solution:
Mix 50 g of Glycerin with freshly boiled water and 5 mL of 0.5 N sodium hydroxide VS. Boil the mixture for 5 min, cool, and add phenolphthalein TS.
Analysis:
Titrate the excess alkali with 0.5 N hydrochloric acid VS. Perform a blank determination (see Titrimetry 541, Residual Titrations).
541, Residual Titrations).
Acceptance criteria:
NMT 1 mL of 0.5 N sodium hydroxide is consumed.
SPECIFIC TESTS
• Color:
When viewed downward against a white surface in a 50-mL color-comparison tube, the color is not darker than the color of a standard made by diluting 0.40 mL of ferric chloride CS with water to 50 mL and similarly viewed in a color-comparison tube of approximately the same diameter and color as that containing the Glycerin.
• Specific Gravity 841:
NLT 1.249
841:
NLT 1.249
• Water Determination, Method I 921:
NMT 5.0%
921:
NMT 5.0%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in tight containers.
• USP Reference Standards 11
11
USP Diethylene Glycol RS 
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USP Ethylene Glycol RS
USP Glycerin RS
1,2,3-Propanetriol.
C3H8O3 92.10
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1,2,3-Propanetriol.
C3H8O3 92.10
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Robert H. Lafaver, M.S.
Scientific Liaison 1-301-816-8335 |
(EXC2010) Monographs - Excipients |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3352
Pharmacopeial Forum: Volume No. 28(4) Page 1245