Sorbitol Sorbitan Solution
Former Title: Anhydrized Liquid Sorbitol
DEFINITION
Sorbitol Sorbitan Solution is a water solution containing, on the anhydrous basis, NLT 25.0% of d-sorbitol (C6H14O6) and NLT 15.0% of 1,4-sorbitan (C6H12O5). The amounts of total sugars, other polyhydric alcohols, and any other 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.
IDENTIFICATION
• A. Procedure
Sample:
1.4 g of Sorbitol Sorbitan Solution in 75 mL of water
Analysis:
Transfer 3 mL of Sample 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, then gently heat the tube in a flame for about 30 s.
Acceptance criteria:
A deep pink or wine-red color appears.
• B.
The retention times of the Sample solution correspond to those 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 Sorbitan Solution to a 25-mL volumetric flask. Add 1.0 mL of Diluent to the flask, and mix on a vortex mixer for about 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 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 Sorbitol Sorbitan 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 Sorbitan Solution.
ASSAY
• Procedure
Mobile phase:
Water
System suitability solution:
10 mg/g of sorbitol, 4 mg/g of 1,4-sorbitan, 4 mg/g of isosorbide, and 1 mg/g of mannitol in water
Standard solution:
10 mg/g of USP Sorbitol RS and 4 mg/g of USP 1,4-Sorbitan RS in water
Sample solution:
Dissolve 0.40 g of Sorbitol Sorbitan Solution in water, and dilute with water to about 20 g. Record the weight of the final solution, and mix thoroughly.
Chromatographic system
Mode:
LC
Detector:
Refractive index
Column:
7.8-mm × 10-cm; packing L34
Temperature
Detector:
35
Column:
50 ± 2
Flow rate:
0.6 mL/min
Injection size:
10 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—The relative retention times for 1,4-sorbitan, isosorbide, mannitol, and sorbitol are about 0.35, 0.43, 0.7, and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 2.0 between 1,4-sorbitan and isosorbide, System suitability solution
Relative standard deviation:
NMT 2.0% for each analyte, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Separately calculate the percentages, on the anhydrous basis, of 1,4-sorbitan and d-sorbitol in the portion of Sorbitol Sorbitan Solution taken:
Result = (rU/rS) × (CS/CU) × [100/(100 - W)] × 100
| rU | = | = peak responses of the corresponding analyte from the Sample solution |
| rS | = | = peak responses of the corresponding analyte from the Standard solution |
| CS | = | = concentration of the appropriate USP Reference Standard in the Standard solution (mg/g) |
| CU | = | = concentration of Sorbitol Sorbitan Solution in the Sample solution (mg/g) |
| W | = | = percentage from the test for Water Determination |
Acceptance criteria:
NLT 25.0% of C6H14O6 and NLT 15.0% of C6H12O5 on the anhydrous basis
IMPURITIES
Inorganic Impurities
• Residue on Ignition 281:
NMT 0.20%, calculated on the anhydrous basis on a 2-g portion
281:
NMT 0.20%, calculated on the anhydrous basis on a 2-g portion
• Limit of Nickel
Solution A:
A saturated ammonium pyrrolidine dithiocarbamate solution (10 mg/mL of ammonium pyrrolidine dithiocarbamate)
Sample solution:
200 mg/mL of Sorbitol Sorbitan Solution in diluted acetic acid. To 100 mL of this solution 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:
Prepare as directed for the 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 the Sample solution, except to omit the use of Sorbitol Sorbitan Solution. Quantities should be increased five fold to ensure that a sufficient volume of Blank solution is available.
Spectrometric conditions
Mode:
Atomic absorption spectrophotometry
Analytical wavelength:
232.0 nm (maximum absorbance)
Lamp:
Nickel hollow-cathode
Flame:
Air–acetylene
Analysis
Samples:
Blank solution, Standard solutions, and Sample 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 ppm, calculated on the anhydrous basis
Organic Impurities
• Procedure: Reducing Sugars
Sample:
An amount of Sorbitol Sorbitan 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 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.
[Note—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 Tests for Specified Organisims 62:
The total aerobic microbial count using the Plate Method is NMT 1000 cfu/mL. The total combined molds and yeasts count is NMT 100 cfu/mL.
61 and Tests for Specified Organisims 62:
The total aerobic microbial count using the Plate Method is NMT 1000 cfu/mL. The total combined molds and yeasts count is NMT 100 cfu/mL.
• pH 791:
4.0–7.0, in a 14% solution of Sorbitol Sorbitan Solution in carbon dioxide-free water
791:
4.0–7.0, in a 14% solution of Sorbitol Sorbitan Solution in carbon dioxide-free water
• Water Determination, Method I 921:
NMT 31.5%
921:
NMT 31.5%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers. No storage requirements specified.
• Labeling:
The labeling indicates the percentage content, on the anhydrous basis, of d-sorbitol and 1,4-sorbitan.
• USP Reference Standards 11
11
USP Diethylene Glycol RS 
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USP Ethylene Glycol RS
USP 1,4-Sorbitan RS
C6H12O5 164.16
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C6H12O5 164.16
USP Sorbitol RS
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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 1968
Pharmacopeial Forum: Volume No. 31(6) Page 1671