Printed on: Thu Jul 15 2021, 06:45:43 PM Official Status: Currently Official on 15-Jul-2021 DocId: 1_GUID-6A5A5AD2-0762-4830-8E99-D593E5400FF0_4_en-US
(EST)
Printed by: Nguyen Nhan Official Date: Official as of 01-May-2020 Document Type: USP & NF @2021 USPC
1
2,2,2-trichloroethanol is NMT the peak response ratio for
Glycerin 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.
C3H8O3 92.09 ASSAY
1,2,3-Propanetriol; • PROCEDURE
Glycerol [56-81-5]. Sodium periodate solution: Dissolve 60 g of sodium
metaperiodate in sufficient water containing 120 mL of
DEFINITION
0.1 N sulfuric acid to make 1000 mL. Do not heat to dissolve
Glycerin contains NLT 99.0% and NMT 101.0% of C3H8O3,
the periodate. If the solution is not clear, pass through a
calculated on the anhydrous basis. sintered-glass filter. Store the solution in a glass-stoppered,
IDENTIFICATION light-resistant container. Test the suitability of this solution
[NOTE—Compliance is determined by meeting the as follows. Pipet 10 mL into a 250-mL volumetric flask, and
requirements for Identification tests A, B, and C.] dilute with water to volume. To 550 mg of Glycerin
dissolved in 50 mL of water, add 50 mL of the diluted
Change to read: periodate solution with a pipet. For a blank, pipet 50 mL of
the solution into a flask containing 50 mL of water. Allow
• A. ▲SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared the solutions to stand for 30 min, then to each add 5 mL of
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Spectroscopy: 197F▲ (CN 1-May-2020) hydrochloric acid and 10 mL of potassium iodide TS, and
• B. LIMIT OF DIETHYLENE GLYCOL AND ETHYLENE GLYCOL rotate to mix. Allow to stand for 5 min, add 100 mL of
Standard solution: 2.0 mg/mL of USP Glycerin RS, water, and titrate with 0.1 N sodium thiosulfate, shaking
0.050 mg/mL of USP Ethylene Glycol RS, 0.050 mg/mL of continuously and adding 3 mL of starch TS as the endpoint
USP Diethylene Glycol RS, and 0.10 mg/mL of ci is approached. The ratio of the volume of 0.1 N sodium
2,2,2-trichloroethanol (internal standard) in methanol thiosulfate required for the glycerin–periodate mixture to
Sample solution: 50 mg/mL of Glycerin and 0.10 mg/mL that required for the blank should be between 0.750 and
of 2,2,2-trichloroethanol (internal standard) in methanol 0.765.
Chromatographic system Analysis: Transfer 400 mg of Glycerin to a 600-mL beaker,
(See Chromatography á621ñ, System Suitability.) dilute with 50 mL of water, add bromothymol blue TS, and
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Mode: GC acidify with 0.2 N sulfuric acid to a definite green or
Detector: Flame ionization greenish yellow color. Neutralize with 0.05 N sodium
Column: 0.53-mm × 30-m fused-silica analytical column hydroxide to a definite blue endpoint, free from green
coated with 3.0-µm G43 stationary phase, and a color. Prepare a blank containing 50 mL of water, and
deactivated split liner with glass wool neutralize in the same manner. Pipet 50 mL of the Sodium
Temperature periodate solution into each beaker, mix by swirling gently,
O
Injector: 220° cover with a watch glass, and allow to stand for 30 min at
Detector: 250° room temperature (not exceeding 35°) in the dark or in
Column: See the temperature program table. 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
Dilute each solution with water to 300 mL, and titrate with
Initial Temperature Final at Final 0.1 N sodium hydroxide VS to a pH of 8.1 ± 0.1 for the
Temperature Ramp Temperature Temperature specimen under assay and 6.5 ± 0.1 for the blank, using a
(°) (°/min) (°) (min) pH meter. Each mL of 0.1 N sodium hydroxide, after
100 — 100 4 correction for the blank, is equivalent to 9.210 mg
of C3H8O3.
100 50 120 10 Acceptance criteria: 99.0%–101.0% on the anhydrous
120 50 220 6 basis
IMPURITIES
Carrier gas: Helium INORGANIC IMPURITIES
Injection size: 1.0 µL • Chloride and Sulfate, Chloride á221ñ: A 7.0-g portion shows
Flow rate: 4.5 mL/min no more chloride than corresponds to 0.10 mL of 0.020 N
Injection type: Split ratio, about 10:1 hydrochloric acid (NMT 10 ppm).
System suitability • Chloride and Sulfate, Sulfate á221ñ: A 10-g portion shows
Sample: Standard solution no more sulfate than corresponds to 0.20 mL of 0.020 N
[NOTE—The relative retention times for ethylene glycol, sulfuric acid (NMT 20 ppm).
2,2,2-trichloroethanol, diethylene glycol, and • RESIDUE ON IGNITION á281ñ: Heat 50 g in an open, shallow
glycerin are about 0.3, 0.6, 0.8 and 1.0, respectively.] 100-mL porcelain dish until it ignites, and allow it to burn
Suitability requirements without further application of heat in a place free from
Resolution: NLT 1.5 between diethylene glycol and drafts. Cool, moisten the residue with 0.5 mL of sulfuric
glycerin acid, and ignite to constant weight: the weight of the
Analysis residue does not exceed 5 mg (0.01%).
Sample: Sample solution ORGANIC IMPURITIES
Acceptance criteria: If a peak at the retention times for the • Procedure 1: Related Compounds
diethylene glycol or ethylene glycol is present in the Sample System suitability solution: 0.5 mg/mL each of USP
solution, the peak response ratio relative to Diethylene Glycol RS and USP Glycerin RS
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Printed by: Nguyen Nhan Official Date: Official as of 01-May-2020 Document Type: USP & NF @2021 USPC
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Sample solution: 50 mg/mL of Glycerin Total impurities: NMT 1.0%
Chromatographic system • Procedure 2: Limit of Chlorinated Compounds
(See Chromatography á621ñ, System Suitability.) Sample: 5 g of Glycerin
Mode: GC Analysis: Transfer the Sample into a dry, round-bottom,
Detector: Flame ionization 100-mL flask. Add 15 mL of morpholine, and connect the
Column: 0.53-mm × 30-m fused-silica analytical column flask by a ground joint to a reflux condenser. Reflux gently
coated with 3.0-µm G43 stationary phase, and an inlet liner for 3 h. Rinse the condenser with 10 mL of water, receiving
having an inverted cup or spiral structure the washings in the flask, and cautiously acidify with nitric
Temperature acid. Transfer the solution to a suitable comparison tube, add
Injector: 220° 0.50 mL of silver nitrate TS, and dilute with water to 50.0 mL.
Detector: 250° Acceptance criteria: The turbidity is not greater than that of a
Column: See the temperature program table below. blank to which 0.20 mL of 0.020 N hydrochloric acid has
been added, the refluxing being omitted (NMT 30 ppm
Hold Time
of Cl).
Initial Temperature Final at Final • Procedure 3: Fatty Acids and Esters
Temperature Ramp Temperature Temperature Sample solution: Mix 50 g of Glycerin with 50 mL of freshly
(°) (°/min) (°) (min) boiled water and 5 mL of 0.5 N sodium hydroxide VS. Boil
100 — 100 — the mixture for 5 min, cool, and add phenolphthalein TS.
Analysis: Titrate the excess alkali with 0.5 N hydrochloric acid
100 7.5 220 4 VS. Perform a blank determination (see Titrimetry á541ñ,
Residual Titrations).
Carrier gas: Helium Acceptance criteria: NMT 1 mL of 0.5 N sodium hydroxide
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Injection size: 0.5 µL is consumed.
Linear velocity: 38 cm/s
Injection type: Split ratio, about 10:1 SPECIFIC TESTS
System suitability • COLOR: When viewed downward against a white surface in a
Sample: System suitability solution 50-mL color-comparison tube, the color is not darker than
Suitability requirements
ci the color of a standard made by diluting 0.40 mL of ferric
Resolution: NLT 7.0 between diethylene glycol and chloride CS with water to 50 mL and similarly viewed in a
glycerin color-comparison tube of approximately the same diameter
Analysis and color as that containing the Glycerin.
Sample: Sample solution • SPECIFIC GRAVITY á841ñ: NLT 1.249
Calculate the percentage of each impurity, excluding any • WATER DETERMINATION, Method I á921ñ: NMT 5.0%
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solvent peaks and diethylene glycol, in the portion of ADDITIONAL REQUIREMENTS
Glycerin taken: • PACKAGING AND STORAGE: Preserve in tight containers.
• USP REFERENCE STANDARDS á11ñ
Result = (rU/rT) × 100 USP Diethylene Glycol RS
USP Ethylene Glycol RS
rU = peak response of each individual impurity from USP Glycerin RS
O
the Sample solution 1,2,3-Propanetriol.
rT = sum of the responses of all the peaks from the C3H8O3 92.10
Sample solution
Acceptance criteria
Individual impurities: NMT 0.1%
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