Noncrystallizing Sorbitol Solution
DEFINITION
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.
IDENTIFICATION
• 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.
[Note—Acetone is used to precipitate sorbitol. ]
Chromatographic system
(See Chromatography 
621
, System Suitability.)
621, System Suitability.)
Mode:
GC
Detector:
Flame ionization
Column:
0.32-mm × 15-m fused-silica capillary column; 0.25-µm layer of phase G46
Temperature
Detector:
300
Injector port:
240
Column:
See the temperature program table below.
| Initial Temperature ( ) |
Temperature Ramp ( /min) |
Final Temperature ( ) |
Hold Time at Final Temperature (min) |
|---|---|---|---|
| 70 | — | 70 | 2 |
| 70 | 50 | 300 | 5 |
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. [Note—A split liner, deactivated with glass wool, is used. ]
System suitability
Sample:
Standard solution
[Note—Diethylene glycol elutes after ethylene glycol in the chromatogram ]
Suitability requirements
Resolution:
NLT 30 between ethylene glycol and diethylene glycol
Analysis
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.
Acceptance criteria
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.
ASSAY
• Procedure
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.
Chromatographic system
Mode:
LC
Detector:
Refractive index
Column:
7.8-mm × 10-cm; packing L34
Temperature
Detector:
35
Column:
50 ± 2
Flow rate:
0.7 mL/min
Injection size:
10 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times for mannitol and sorbitol are about 0.6 and 1.0, respectively, System suitability solution. ]
Suitability requirements
Resolution:
NLT 2.0 between sorbitol and mannitol, System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
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
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Sorbitol RS in the Standard solution (mg/g) |
| CU | = | = concentration of Noncrystallizing Sorbitol Solution in the Sample solution (mg/g) |
Acceptance criteria:
NLT 45.0%
IMPURITIES
Inorganic Impurities
• Residue on Ignition 281:
NMT 0.1%, calculated on the anhydrous basis, determined on a 2-g portion
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.
Spectrometric conditions
Mode:
Atomic absorption spectrophotometry
Analytical wavelength:
232.0 nm (maximum absorbance)
Lamp:
Nickel hollow-cathode
Flame:
Air–acetylene
Analysis
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
Organic Impurities
• 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.
SPECIFIC TESTS
• 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.
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:
5.0–7.5, in a 14% (w/w) solution of Noncrystallizing Sorbitol Solution in carbon dioxide-free water
791:
5.0–7.5, in a 14% (w/w) solution of Noncrystallizing Sorbitol Solution in carbon dioxide-free water
• Water Determination, Method I 921:
28.5%–31.5%
921:
28.5%–31.5%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers. No storage requirements are specified.
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Robert H. Lafaver, M.S.
Scientific Liaison 1-301-816-8335 |
(EXC2010) Monographs - Excipients |
| 61 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 62 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 1966
Pharmacopeial Forum: Volume No. 30(3) Page 995