11/7/2020 USP-NF Glycerin

Printed on: Sat Nov 07 2020, 11:17:06 am

Printed by: Shruti Kharidia
O cial Status: Currently O cial on 07-Nov-2020
O cial Date: O cial as of 1-May-2020
Document Type: USP & NF
DocId: 1_GUID-6A5A5AD2-0762-4830-8E99-D593E5400FF0_4_en-US
Printed from: https://online.uspnf.com/uspnf/document/1_GUID-6A5A5AD2-0762-4830-8E99-D593E5400FF0_4_en-US
© 2020 USPC

Glycerin

C3H8O3 92.09
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 Identi cation tests A, B, and C.]
Change to read:
• A. ▲SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉, Infrared Spectroscopy: 197F▲ (CN 1-MAY-2020)
• 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
(See Chromatography 〈621〉, System Suitability.)
Mode: GC
L
IA
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
IC

Injector: 220°
Detector: 250°
Column: See the temperature program table.

Hold Time at Final

FF

Initial Temperature (°) Temperature Ramp (°/min) Final Temperature (°) Temperature (min)

100 — 100 4

100 50 120 10
O

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.

https://online.uspnf.com/uspnf/document/1_GUID-6A5A5AD2-0762-4830-8E99-D593E5400FF0_4_en-US?source=TOC 1/3
11/7/2020 USP-NF Glycerin

• C. Examine the chromatograms obtained in Identi cation 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 su cient 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 lter. 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 ask, 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 ask 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 de nite green or greenish yellow color. Neutralize with 0.05 N sodium hydroxide to a de nite 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.
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).

L
• 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).
IA
• 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%).
ORGANIC IMPURITIES
IC

• 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
(See Chromatography 〈621〉, System Suitability.)
FF

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
O

Injector: 220°
Detector: 250°
Column: See the temperature program table below.

Hold Time at Final

Initial Temperature (°) Temperature Ramp (°/min) Final Temperature (°) 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

https://online.uspnf.com/uspnf/document/1_GUID-6A5A5AD2-0762-4830-8E99-D593E5400FF0_4_en-US?source=TOC 2/3
11/7/2020 USP-NF 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 ask. Add 15 mL of morpholine, and connect the ask by a ground
joint to a re ux condenser. Re ux gently for 3 h. Rinse the condenser with 10 mL of water, receiving the washings in the ask, 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 re uxing being omitted (NMT 30 ppm of Cl).
• PROCEDURE 3: FATTY ACIDS AND ESTERS
Sample solution: Mix 50 g of Glycerin with 50 mL of 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).
Acceptance criteria: NMT 1 mL of 0.5 N sodium hydroxide is consumed.

SPECIFIC TESTS
L
• 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
IA
approximately the same diameter and color as that containing the Glycerin.
• SPECIFIC GRAVITY 〈841〉: NLT 1.249
• WATER DETERMINATION, Method I〈921〉: NMT 5.0%

ADDITIONAL REQUIREMENTS
IC

• PACKAGING AND STORAGE: Preserve in tight containers.

• USP REFERENCE STANDARDS 〈11〉
USP Diethylene Glycol RS
USP Ethylene Glycol RS
USP Glycerin RS
FF

1,2,3-Propanetriol.
C3H8O3 92.10

Auxiliary Information- Please check for your question in the FAQs before contacting USP.
O

Topic/Question Contact Expert Committee

GLYCERIN Tong Liu SE2020 Simple Excipients

Senior Scienti c Liaison

Chromatographic Database Information: Chromatographic Database

Most Recently Appeared In:

Pharmacopeial Forum: Volume No. 28(4)

Page Information:

USP43-NF38 - 2132
USP42-NF37 - 2084
USP41-NF36 - 1967

Current DocID: GUID-6A5A5AD2-0762-4830-8E99-D593E5400FF0_4_en-US

https://online.uspnf.com/uspnf/document/1_GUID-6A5A5AD2-0762-4830-8E99-D593E5400FF0_4_en-US?source=TOC 3/3