Printed on: Mon May 30 2022, 08:57:24 AM(EST) Official Status: Currently Official on 30-May-2022 DocId: 1_GUID-6A5A5AD2-0762-4830-8E99-D593E5400FF0_4_en-US

Printed by: kkl farmakopi Official Date: Official as of 01-May-2020 Document Type: USP & NF @2022 USPC
DOI Ref: a6ixg DOI: https://doi.org/10.31003/USPNF_M35420_04_01
1

2,2,2-trichloroethanol in the Standard solution; NMT 0.10%

Glycerin 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
C3H8O3 92.09 Standard solution.
1,2,3-Propanetriol; ASSAY
Glycerol CAS RN®: 56-81-5. • PROCEDURE
Sodium periodate solution: Dissolve 60 g of sodium
DEFINITION
metaperiodate in sufficient water containing 120 mL of
Glycerin contains NLT 99.0% and NMT 101.0% of C3H8O3,
0.1 N sulfuric acid to make 1000 mL. Do not heat to dissolve
calculated on the anhydrous basis. the periodate. If the solution is not clear, pass through a
IDENTIFICATION sintered-glass filter. Store the solution in a glass-stoppered,
[NOTE—Compliance is determined by meeting the light-resistant container. Test the suitability of this solution
requirements for Identification tests A, B, and C.] as follows. Pipet 10 mL into a 250-mL volumetric flask, and
dilute with water to volume. To 550 mg of Glycerin
Change to read: dissolved in 50 mL of water, add 50 mL of the diluted
periodate solution with a pipet. For a blank, pipet 50 mL of
• A. ▲SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared the solution into a flask containing 50 mL of water. Allow
Spectroscopy: 197F▲ (CN 1-May-2020) the solutions to stand for 30 min, then to each add 5 mL of
• B. LIMIT OF DIETHYLENE GLYCOL AND ETHYLENE GLYCOL hydrochloric acid and 10 mL of potassium iodide TS, and
Standard solution: 2.0 mg/mL of USP Glycerin RS, rotate to mix. Allow to stand for 5 min, add 100 mL of

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0.050 mg/mL of USP Ethylene Glycol RS, 0.050 mg/mL of water, and titrate with 0.1 N sodium thiosulfate, shaking
USP Diethylene Glycol RS, and 0.10 mg/mL of continuously and adding 3 mL of starch TS as the endpoint
2,2,2-trichloroethanol (internal standard) in methanol is approached. The ratio of the volume of 0.1 N sodium
Sample solution: 50 mg/mL of Glycerin and 0.10 mg/mL thiosulfate required for the glycerin–periodate mixture to
of 2,2,2-trichloroethanol (internal standard) in methanol
ci that required for the blank should be between 0.750 and
Chromatographic system 0.765.
(See Chromatography á621ñ, System Suitability.) Analysis: Transfer 400 mg of Glycerin to a 600-mL beaker,
Mode: GC dilute with 50 mL of water, add bromothymol blue TS, and
Detector: Flame ionization acidify with 0.2 N sulfuric acid to a definite green or
Column: 0.53-mm × 30-m fused-silica analytical column greenish yellow color. Neutralize with 0.05 N sodium
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coated with 3.0-µm G43 stationary phase, and a hydroxide to a definite blue endpoint, free from green
deactivated split liner with glass wool color. Prepare a blank containing 50 mL of water, and
Temperature neutralize in the same manner. Pipet 50 mL of the Sodium
Injector: 220° periodate solution into each beaker, mix by swirling gently,
Detector: 250° cover with a watch glass, and allow to stand for 30 min at
Column: See the temperature program table. room temperature (not exceeding 35°) in the dark or in
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subdued light. Add 10 mL of a mixture of equal volumes of

ethylene glycol and water, and allow to stand for 20 min.
Hold Time
Initial Temperature Final at Final Dilute each solution with water to 300 mL, and titrate with
Temperature Ramp Temperature Temperature 0.1 N sodium hydroxide VS to a pH of 8.1 ± 0.1 for the
(°) (°/min) (°) (min) specimen under assay and 6.5 ± 0.1 for the blank, using a
100 — 100 4 pH meter. Each mL of 0.1 N sodium hydroxide, after
correction for the blank, is equivalent to 9.210 mg
100 50 120 10 of C3H8O3.
120 50 220 6 Acceptance criteria: 99.0%–101.0% on the anhydrous
basis
Carrier gas: Helium IMPURITIES
Injection size: 1.0 µL INORGANIC IMPURITIES
Flow rate: 4.5 mL/min • Chloride and Sulfate, Chloride á221ñ: A 7.0-g portion shows
Injection type: Split ratio, about 10:1 no more chloride than corresponds to 0.10 mL of 0.020 N
System suitability hydrochloric acid (NMT 10 ppm).
Sample: Standard solution • Chloride and Sulfate, Sulfate á221ñ: A 10-g portion shows
[NOTE—The relative retention times for ethylene glycol, no more sulfate than corresponds to 0.20 mL of 0.020 N
2,2,2-trichloroethanol, diethylene glycol, and sulfuric acid (NMT 20 ppm).
glycerin are about 0.3, 0.6, 0.8 and 1.0, respectively.] • RESIDUE ON IGNITION á281ñ: Heat 50 g in an open, shallow
Suitability requirements 100-mL porcelain dish until it ignites, and allow it to burn
Resolution: NLT 1.5 between diethylene glycol and without further application of heat in a place free from
glycerin drafts. Cool, moisten the residue with 0.5 mL of sulfuric
Analysis acid, and ignite to constant weight: the weight of the
Sample: Sample solution residue does not exceed 5 mg (0.01%).
Acceptance criteria: If a peak at the retention times for the ORGANIC IMPURITIES
diethylene glycol or ethylene glycol is present in the Sample • Procedure 1: Related Compounds
solution, the peak response ratio relative to System suitability solution: 0.5 mg/mL each of USP
2,2,2-trichloroethanol is NMT the peak response ratio for Diethylene Glycol RS and USP Glycerin RS
diethylene glycol or ethylene glycol relative to Sample solution: 50 mg/mL of Glycerin

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Printed on: Mon May 30 2022, 08:57:24 AM(EST) Official Status: Currently Official on 30-May-2022 DocId: 1_GUID-6A5A5AD2-0762-4830-8E99-D593E5400FF0_4_en-US
Printed by: kkl farmakopi Official Date: Official as of 01-May-2020 Document Type: USP & NF @2022 USPC
DOI Ref: a6ixg DOI: https://doi.org/10.31003/USPNF_M35420_04_01
2

Chromatographic system Total impurities: NMT 1.0%

(See Chromatography á621ñ, System Suitability.) • Procedure 2: Limit of Chlorinated Compounds
Mode: GC Sample: 5 g of Glycerin
Detector: Flame ionization Analysis: Transfer the Sample into a dry, round-bottom,
Column: 0.53-mm × 30-m fused-silica analytical column 100-mL flask. Add 15 mL of morpholine, and connect the
coated with 3.0-µm G43 stationary phase, and an inlet liner flask by a ground joint to a reflux condenser. Reflux gently
having an inverted cup or spiral structure for 3 h. Rinse the condenser with 10 mL of water, receiving
Temperature the washings in the flask, and cautiously acidify with nitric
Injector: 220° acid. Transfer the solution to a suitable comparison tube, add
Detector: 250° 0.50 mL of silver nitrate TS, and dilute with water to 50.0 mL.
Column: See the temperature program table below. Acceptance criteria: The turbidity is not greater than that of a
blank to which 0.20 mL of 0.020 N hydrochloric acid has
Hold Time been added, the refluxing being omitted (NMT 30 ppm
Initial Temperature Final at Final of Cl).
Temperature Ramp Temperature Temperature • Procedure 3: Fatty Acids and Esters
(°) (°/min) (°) (min) Sample solution: Mix 50 g of Glycerin with 50 mL of freshly
100 — 100 — boiled water and 5 mL of 0.5 N sodium hydroxide VS. Boil
the mixture for 5 min, cool, and add phenolphthalein TS.
100 7.5 220 4 Analysis: Titrate the excess alkali with 0.5 N hydrochloric acid
VS. Perform a blank determination (see Titrimetry á541ñ,
Carrier gas: Helium Residual Titrations).
Injection size: 0.5 µL Acceptance criteria: NMT 1 mL of 0.5 N sodium hydroxide

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Linear velocity: 38 cm/s is consumed.
Injection type: Split ratio, about 10:1
System suitability SPECIFIC TESTS
Sample: System suitability solution • COLOR: When viewed downward against a white surface in a
Suitability requirements 50-mL color-comparison tube, the color is not darker than
Resolution: NLT 7.0 between diethylene glycol and
ci the color of a standard made by diluting 0.40 mL of ferric
glycerin chloride CS with water to 50 mL and similarly viewed in a
Analysis color-comparison tube of approximately the same diameter
Sample: Sample solution and color as that containing the Glycerin.
Calculate the percentage of each impurity, excluding any • SPECIFIC GRAVITY á841ñ: NLT 1.249
solvent peaks and diethylene glycol, in the portion of • WATER DETERMINATION, Method I á921ñ: NMT 5.0%
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Glycerin taken: ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight containers.
Result = (rU/rT) × 100 • USP REFERENCE STANDARDS á11ñ
USP Diethylene Glycol RS
rU = peak response of each individual impurity from USP Ethylene Glycol RS
the Sample solution USP Glycerin RS
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rT = sum of the responses of all the peaks from the 1,2,3-Propanetriol.

Sample solution C3H8O3 92.10
Acceptance criteria
Individual impurities: NMT 0.1%

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