Glycerin (glis' er in). DEFINITION Glycerin contains NLT 99.0% and NMT 101.0% of C3H8O3, calculated on the anhydrous basis. IDENTIFICATION [NoteCompliance 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.
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 [NoteThe 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 glycerinperiodate 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. 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). • 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). • Heavy Metals 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%). 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.
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
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). 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 • Water Determination, Method I 921: NMT 5.0% ADDITIONAL REQUIREMENTS • Packaging and Storage: Preserve in tight containers. • USP Reference Standards 11 USP Ethylene Glycol RS Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 3352 Pharmacopeial Forum: Volume No. 28(4) Page 1245Chromatographic Column Chromatographic columns text is not derived from, and not part of, USP 35 or NF 30. |