Noncrystallizing Sorbitol Solution
Noncrystallizing Sorbitol Solution is an aqueous solution containing NLT 45.0% of d-sorbitol (C6H14O6) (w/w). The amounts of total sugars, other polyhydric alcohols, and any hexitol anhydrides, if detected, are not included in the requirements nor 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 Noncrystallizing Sorbitol Solution in 75 mL of water.
Analysis: Transfer 3 mL of 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 from 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 Noncrystallizing 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 the 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 Noncrystallizing 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 Noncrystallizing Sorbitol Solution.
Mobile phase: Use degassed water.
System suitability solution: 4.8 mg/g each of mannitol and USP Sorbitol RS
Standard solution: 4.8 mg/g of USP Sorbitol RS
Sample solution: Weigh 0.20 g of Noncrystallizing Sorbitol Solution, and dissolve in and dilute with water to 20 g. Record the final solution weight.
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 about 0.6 and 1.0, respectively, System suitability solution. ]
Resolution: NLT 2.0 between sorbitol and mannitol, System suitability solution
Relative standard deviation: NMT 2.0%, Standard solution
Samples: Standard solution and Sample solution
Calculate the percentage of d-sorbitol (C6H14O6) in the portion of Noncrystallizing Sorbitol Solution taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria: NLT 45.0%
• 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 20.0 g of Noncrystallizing Sorbitol Solution in diluted acetic acid, and dilute with diluted acetic acid to 100.0 mL. 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.
Blank solution: Prepare as directed for the Sample solution, except omit the use of the Noncrystallizing Sorbitol Solution.
Standard solutions: Prepare as directed for the Sample solution, except prepare three solutions by adding 0.5, 1.0, and 1.5 mL of nickel standard solution TS.
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 the Standard solutions and the Sample solution. 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 µg/g on the anhydrous basis
• Procedure: Reducing Sugars
Sample: An amount of Noncrystallizing Sorbitol Solution, equivalent to 3.3 g on the anhydrous basis.
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 towards 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. The 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.
• Microbial Enumeration Tests 61 and Absence of Specified Microorganisms 62: The total aerobic microbial count using the Plate Method is NMT 1000 cfu/mL, and the total combined molds and yeasts count is NMT 100 cfu/mL.
• pH 791: 5.07.5, in a 14% (w/w) solution of Noncrystallizing 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 are specified.
• USP Reference Standards 11
USP Ethylene Glycol RS
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USP35NF30 Page 1966Pharmacopeial Forum: Volume No. 30(3) Page 995