Sorbitol Solution is an aqueous solution containing NLT 64.0% of d-sorbitol (C6H14O6). The amounts of total sugars, other polyhydric alcohols, and any hexitol anhydrides, if detected, are not included in the requirements or in the calculated amount under General Notices, 5.60.10. Other Impurities in USP and NF Articles.
• A. Procedure
Sample solution: Dissolve 1.4 g of Sorbitol Solution in 75 mL of water.
Analysis: Transfer 3 mL of the Sample solution to a 15-cm test tube. Add 3 mL of freshly prepared catechol solution (1 in 10), and mix. Add 6 mL of sulfuric acid, mix again, and gently heat the tube in a flame for 30 s.
Acceptance criteria: A deep pink or wine-red color appears.
• B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
• C. Limit of Diethylene Glycol and Ethylene Glycol
Diluent: Acetone and water (96:4)
Standard solution: 0.08 mg/mL of USP Diethylene Glycol RS and 0.08 mg/mL of USP Ethylene Glycol RS in Diluent
Sample solution: Transfer 2.0 g of Sorbitol Solution to a 25-mL volumetric flask. Add 1.0 mL of Diluent to the flask, and mix on a vortex mixer for 3 min. Add the remaining Diluent to the flask to volume in three equal portions. Mix on a vortex mixer for about 3 min after each addition of Diluent. Pass a portion of the supernatant layer obtained through a 0.45-µm nylon filter. Discard the first 2 mL of the filtrate, and collect the rest of the filtrate for analysis. [NoteAcetone is used to precipitate sorbitol. ]
(See Chromatography 621, System Suitability.)
Detector: Flame ionization
Column: 0.32-mm × 15-m fused-silica capillary column; 0.25-µm layer of phase G46
Injector port: 240
Column: See the temperature program table below.
Carrier gas: Helium
Flow rate: 3.0 mL/min
Injection size: 1.0 µL
Injection type: Split injection. The split ratio is about 10:1. [NoteA split liner, deactivated with glass wool, is used. ]
Sample: Standard solution
[NoteDiethylene glycol elutes after ethylene glycol in the chromatogram. ]
Resolution: NLT 30 between ethylene glycol and diethylene glycol
Samples: Standard solution and Sample solution
Based on the Standard solution, identify the peaks of ethylene glycol and diethylene glycol. Compare peak areas of ethylene glycol and diethylene glycol in the Standard solution and the Sample solution.
Diethylene glycol: The peak area of diethylene glycol in the Sample solution is NMT the peak area of diethylene glycol in the Standard solution, corresponding to NMT 0.10% of diethylene glycol in Sorbitol Solution.
Ethylene glycol: The peak area of ethylene glycol in the Sample solution is NMT the peak area of ethylene glycol in the Standard solution, corresponding to NMT 0.10% of ethylene glycol in Sorbitol Solution.
Mobile phase: Water
System suitability solution: 4.8 mg/g of mannitol and 4.8 mg/g of USP Sorbitol RS in water
Standard solution: 4.8 mg/g of USP Sorbitol RS in water
Sample solution: 6.0 mg/g of Sorbitol Solution in water
Detector: Refractive index
Column: 7.8-mm × 10-cm; packing L34
Column: 50 ± 2
Flow rate: 0.7 mL/min
Injection size: 10 µL
Samples: System suitability solution and Standard solution
[NoteThe relative retention times for mannitol and sorbitol are 0.6 and 1.0, respectively. ]
Resolution: NLT 2.0 between sorbitol and mannitol, System suitability solution
Relative standard deviation: NMT 2.0% for sorbitol, Standard solution
Samples: Standard solution and Sample solution
Calculate the percentage of C6H14O6 in the Sorbitol Solution taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria: NLT 64.0%
• Residue on Ignition 281: NMT 0.1%, calculated on the anhydrous basis, determined on a 2-g portion
• Limit of Nickel
Solution A: A saturated ammonium pyrrolidine dithiocarbamate solution (containing 10 mg/mL of ammonium pyrrolidine dithiocarbamate)
Sample solution: Dissolve and dilute 20.0 g of Sorbitol Solution to 100 mL with diluted acetic acid. Add 2.0 mL of Solution A and 10.0 mL of methyl isobutyl ketone, and shake for 30 s. Protect from bright light. Allow the two layers to separate, and use the methyl isobutyl ketone layer.
Standard solutions: Prepared as directed for Sample solution, except to prepare three solutions by adding 0.5, 1.0, and 1.5 mL of nickel standard solution TS.
Blank solution: Prepare as directed for Sample solution, except to omit the use of the Sorbitol Solution.
Mode: Atomic absorption spectrophotometry
Analytical wavelength: 232.0 nm (maximum absorbance)
Lamp: Nickel hollow-cathode
Samples: Standard solutions, Sample solution, and Blank solution
Set the instrument to zero using the Blank solution. Concomitantly determine the absorbances of the Standard solutions and the Sample solution at least three times each. Record the average of the steady readings for each of these solutions. Between each measurement, aspirate the Blank solution, and ascertain that the reading returns to zero. Plot the absorbances of the Standard solutions and the Sample solution versus the added quantity of nickel. Extrapolate the line joining the points on the graph until it meets the concentration axis. The distance between this point and the intersection of the axes represents the concentration of nickel in the Sample solution.
Acceptance criteria: NMT 1 ppm, calculated on the anhydrous basis
• Procedure: Reducing Sugars
Sample: Equivalent to 3.3 g of sorbitol on the anhydrous basis from Sorbitol Solution
Analysis: To the Sample, add 3 mL of water, 20.0 mL of cupric citrate TS, and a few glass beads. Heat so that boiling begins after 4 min, and maintain boiling for 3 min. Cool rapidly, and add 40 mL of diluted acetic acid, 60 mL of water, and 20.0 mL of 0.05 N iodine VS. With continuous shaking, add 25 mL of a mixture of 6 mL of hydrochloric acid and 94 mL of water. When the precipitate has dissolved, titrate the excess of iodine with 0.05 N sodium thiosulfate VS using 2 mL of starch TS, added toward the end of the titration, as an indicator.
Acceptance criteria: NLT 12.8 mL of 0.05 N sodium thiosulfate VS is required, corresponding to NMT 0.3% of reducing sugars, on the anhydrous basis, as glucose. [NoteThe amount determined in this test is not included in the calculated amount under General Notices, 5.60.10. Other Impurities in USP and NF Articles. ]
• pH 791: 5.07.5, in a 14% (w/w) solution of Sorbitol Solution in carbon dioxide-free water
• Water Determination, Method I 921: 28.5%31.5%
• Packaging and Storage: Preserve in well-closed containers. No storage requirements specified.
• USP Reference Standards 11
USP Ethylene Glycol RS
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USP35NF30 Page 4675Pharmacopeial Forum: Volume No. 30(3) Page 929