Sorbitol
C6H14O6 182.17
d-Glucitol
[50-70-4].
(sor' bi tol).
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C6H14O6 182.17
d-Glucitol
[50-70-4].DEFINITION
Sorbitol contains NLT 91.0% and NMT 100.5% of d-sorbitol, calculated on the anhydrous basis. 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 Other Impurities in General Notices.
IDENTIFICATION
• A.
Sample solution:
1 g of Sorbitol in 75 mL of water
Analysis:
Transfer 3 mL of Sample solution to a 15-cm test tube, and add 3 mL of freshly prepared catechol solution (1 in 10), and mix. Add 6 mL of sulfuric acid, then 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 from the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Mobile phase:
Use degassed water.
System suitability solution:
Prepare a solution containing 4.8 mg/g of each USP Sorbitol RS and mannitol
Standard solution:
4.8 mg/g of USP Sorbitol RS
Sample solution:
Dissolve 0.10 g of Sorbitol in water, and dilute with water to 20 g. Record the final solution weight, and mix thoroughly.
Chromatographic system
Mode:
LC
Detector:
Refractive index
Column:
7.8-mm × 10-cm; packing L34
Temperature
Column:
50 ± 2
Detector:
35
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. ]
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, on the anhydrous basis, of d-sorbitol in the portion of Sorbitol taken:
Result = (rU/rS) × (CS/CU) × (100/(100 
W)) × 100
W)) × 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 Sorbitol in the Sample solution (mg/g) |
| W | = | = percentage obtained in the test for Water Determination |
Acceptance criteria:
91.0%–100.5% on the anhydrous basis
IMPURITIES
• Limit of Nickel
Sample solution:
Dissolve 20.0 g of Sorbitol in diluted acetic acid, and dilute with diluted acetic acid to 150 mL.
Blank solution:
150 mL of diluted acetic acid
Standard solutions:
Prepare three solutions by adding 0.5, 1.0, and 1.5 mL of nickel standard solution TS to 20.0 g of Sorbitol dissolved in diluted acetic acid, and dilute with the same solvent to 150 mL.
Instrumental conditions
Mode:
Atomic absorption spectrophotometry
Analytical wavelength:
232.0 nm
Lamp:
Nickel hollow-cathode
Flame:
Air–acetylene
Analysis
Samples:
Standard solutions and Sample solution
To each sample add 2.0 mL of a saturated ammonium pyrrolidinedithiocarbamate solution (containing 10 g/L of ammonium pyrrolidinedithiocarbamate) 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. Set the instrument to zero using the organic layer from the Blank solution. Concomitantly determine the absorbances of the organic layer from the Samples 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 organic layer from 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
• Residue on Ignition 
281
:
NMT 0.1%, determined on a 1.5-g portion
281:
NMT 0.1%, determined on a 1.5-g portion
• Reducing Sugars
[Note—The amount determined in this test is not included in the calculated amount under Other Impurities in the General Notices. ]
Sample solution:
Dissolve 3.3 g of Sorbitol in 3 mL of water with the aid of gentle heat. Cool, and add 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.
Analysis:
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, as glucose.
• Chloride and Sulfate, Chloride 221 (if labeled for use in preparing parenteral dosage forms)
221 (if labeled for use in preparing parenteral dosage forms)
Sample:
1.5 g
Acceptance criteria:
The Sample shows no more chloride than corresponds to 0.10 mL of 0.020 N hydrochloric acid (NMT 0.0050%).
• Chloride and Sulfate, Sulfate 221 (if labeled for use in preparing parenteral dosage forms)
221 (if labeled for use in preparing parenteral dosage forms)
Sample:
1.0 g
Acceptance criteria:
The Sample shows no more sulfate than corresponds to 0.10 mL of 0.020 N sulfuric acid (NMT 0.01%).
SPECIFIC TESTS
• Microbial Enumeration Tests 61 and Tests for Specified Microorganisms 62:
The total aerobic count using the Plate Method is NMT 1000 cfu/g, and the total combined molds and yeasts count is NMT 100 cfu/g.
61 and Tests for Specified Microorganisms 62:
The total aerobic count using the Plate Method is NMT 1000 cfu/g, and the total combined molds and yeasts count is NMT 100 cfu/g.
• pH 791:
3.5–7.0, in a 10% (w/w) solution in carbon dioxide-free water
791:
3.5–7.0, in a 10% (w/w) solution in carbon dioxide-free water
• Water Determination, Method I 921:
NMT 1.5%
921:
NMT 1.5%
• Clarity and Color of Solution (if labeled for use in preparing parenteral dosage forms)
Sample:
10.0 g
Analysis:
Dissolve the Sample in 100.0 mL of carbon dioxide-free water.
Acceptance criteria:
The solution is clear and colorless.
• Bacterial Endotoxins Test 85 (if labeled for use in preparing parenteral dosage forms):
NMT 4 USP Endotoxin Units/g for parenteral dosage forms having a concentration of less than 100 g/L of sorbitol, and NMT 2.5 USP Endotoxin Units/g for parenteral dosage forms having a concentration of 100 g/L or more of sorbitol
85 (if labeled for use in preparing parenteral dosage forms):
NMT 4 USP Endotoxin Units/g for parenteral dosage forms having a concentration of less than 100 g/L of sorbitol, and NMT 2.5 USP Endotoxin Units/g for parenteral dosage forms having a concentration of 100 g/L or more of sorbitol
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers. No storage requirements are specified.
• Labeling:
Sorbitol intended for use in preparing parenteral dosage forms is so labeled.
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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 |
| 85 |
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 1965
Pharmacopeial Forum: Volume No. 30(3) Page 992