Sorbitol Solution

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

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 nor in the calculated amount as stated in General Notices, 5.60.10 Other Impurities in USP and NF Articles.

2 IDENTIFICATION

A.

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 a freshly prepared solution of catechol (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 3 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.)

Mode: GC

Detector: Flame ionization

Column: 0.32-mm × 15-m fused-silica capillary column; 0.25-µm layer of phase G46

Temperatures

Detector: 300°

Injection port: 240° Column: See Table 1.

Table 1

Carrier gas: Helium Flow rate: 3.0 mL/min Injection volume: 1.0 µL

Injection type: Split, split ratio 10:1. [NOTE—A split liner, deactivated with glass wool, is used.]

System suitability

Sample: Standard solution

[NOTE—Diethylene glycol elutes after ethylene glycol.]

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 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.

3 ASSAY

PROCEDURE

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

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Refractive index

Column: 7.8-mm × 10-cm; packing L34

Temperatures

Detector: 35°

Column: 50 ± 2°

Flow rate: 0.7 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE—The relative retention times for mannitol and sorbitol are 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% for sorbitol, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of D-sorbitol (C₆H₁₄O₆) in the portion of Sorbitol Solution taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of sorbitol from the Sample solution

r_S = peak response of sorbitol from the Standard solution

C_S = concentration of USP Sorbitol RS in the Standard solution (mg/g)

C_U = concentration of Sorbitol Solution in the Sample solution (mg/g)

Acceptance criteria: NLT 64.0%

4 IMPURITIES

RESIDUE ON IGNITION 〈281〉: NMT 0.1%, calculated on the anhydrous basis, determined on a 2-g portion

Change to read:

LIMIT OF NICKEL

[NOTE—When water is specified as the diluent, use deionized ultra-filtered water. Use of glass volumetric flasks is discouraged.] Digest solution: Add 360 mL of hydrochloric acid, ultratrace, and 240 mL of nitric acid, ultratrace, to 1200 mL of water.

Blank solution: Add 40 mL of nitric acid, ultratrace, to a 2000-mL volumetric flask, dilute with water to volume, and mix well.

Internal standard solution: Transfer 2.0 mL of solution containing 1000 mg/L of yttrium1 to a 1000-mL volumetric flask, dilute with Blank solution to volume, and mix well. The Internal standard solution contains 2 µg/mL of yttrium. [NOTE—The concentration of the Internal standard solution can be adjusted if a high number of signal counts from the Internal standard solution causes an artifact.]

Standard stock solution: [NOTE—Prepare this solution fresh every 2 months.] Quantitatively dilute an accurately measured volume of the solution containing 1000 mg/L of nickel2 with Blank solution to obtain a solution containing 10 µg/mL of nickel.

Standard nickel solution A: [NOTE—Prepare this solution fresh weekly.] Pipet 1.0 mL of Standard stock solution into a 200-mL volumetric flask.

Dilute the content in the flask with Blank solution to volume, and mix well. This solution contains 50 ng/mL of nickel.

Standard nickel solution B: [NOTE—Prepare this solution fresh weekly.] Pipet 2.0 mL of Standard stock solution into a 200-mL volumetric flask. Dilute the content in the flask with Blank solution to volume, and mix well. This solution contains 100 ng/mL of nickel.

Standard nickel solution C: [NOTE—Prepare this solution fresh weekly.] Pipet 4.0 mL of Standard stock solution into a 200-mL volumetric flask. Dilute the content in the flask with Blank solution to volume, and mix well. This solution contains 200 ng/mL of nickel.

Sample solution: Transfer a quantity of Sorbitol Solution, equivalent to 10.0 g on the anhydrous basis, into a 125-mL conical flask. Add 40 mL of Digest solution, and place on a hot plate. Heat the solution for about 20 min, being careful to prevent the solution from boiling over. Pull the sample off the hot plate just before it turns a dark caramel color. [NOTE—Do not overburn the sample.] Transfer the flask's contents into a clean, dry, 50-mL volumetric flask with washings of Blank solution. Dilute with Blank solution to volume. Filter the sample into a 15-mL centrifuge tube, using a 10-mL disposable syringe fitted with a syringe filter of 0.45-µm pore size.

Instrumental conditions

(See Plasma Spectrochemistry 〈730〉.) Mode: ICP–OES

Emission wavelengths: 232.005 nm for nickel and 371.029 nm for yttrium. Set the sample read time and other instrument parameters as appropriate or as recommended by the instrument manufacturer.

System suitability

Samples: Blank solution, Standard nickel solution A, Standard nickel solution B, and Standard nickel solution C Suitability requirements

[NOTE—Instrument performance must be verified to conform to the manufacturer's specifications for resolution and sensitivity. Before analyzing samples, the instrument must pass a suitable performance check.]

Correlation coefficient: NLT 0.999, determined from the Calibration curve constructed in the Analysis Analysis

Samples: Blank solution, Standard nickel solution A, Standard nickel solution B, and Standard nickel solution C, and Sample solution [NOTE—The following analysis is described for one type of ICP–OES instruments. If a different ICP–OES instrument is used, follow the instrument manufacturer's recommendations for operation.]

Take 3 replicate scans with the integration set as recommended by the instrument manufacturer. Follow the instrument manufacturer's recommendations for delivering the sample. Add the Internal standard solution in-line via a mixing block between the sample probe and the spray chamber. Flush the samples through the system before analysis. Program a read delay into the sampling routine to allow for fluid flow equilibration after the high-speed flush, before the first analytical read of the sample. Between samples, wash the pumping system by flushing the Blank solution.

Calibration curve: Generate the calibration curve using the Blank solution, Standard nickel solution A, Standard nickel solution B, and Standard nickel solution C as follows. Scan the Internal standard solution while running the Blank solution to measure the intensity of the yttrium emission. Hold this value constant throughout the remainder of the test. Separately scan the Blank solution, Standard nickel solution A, Standard nickel solution B, and Standard nickel solution C for nickel and yttrium. [NOTE—Add the Internal standard solution via an in-line mixing chamber.] Normalize the yttrium intensity to the value of the Internal standard solution. Apply this normalization factor to the nickel intensity, which is then referred to as the corrected nickel intensity. Construct a calibration curve by plotting the corrected nickel intensity versus the known concentrations, in ng/mL, of nickel.

Similarly, analyze the Sample solution. Plot the intensity of the emission of the Sample solution on the calibration curve. Determine the concentration of nickel (C), in ng/mL, in the Sample solution through the calibration curve. Calculate the content, in µg/g, of nickel in the solid portion of Sorbitol Solution taken:

Result = (F × V × C)/W

F = conversion factor, 10–3 µg/ng (ng to µg)

V = volume of the Sample solution, 50 mL

C = concentration of nickel in the Sample solution (ng/mL)

W = weight of Sorbitol Solution calculated on the anhydrous basis (g) Acceptance criteria: NMT 1 µg/g (USP 1-May-2021)

REDUCING SUGARS

[NOTE—The amount determined in this test is not included in the calculated amount as requested in General Notices, 5.60.10 Other Impurities in USP and NF Articles .]

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 the 0.05 N sodium thiosulfate VS is required, corresponding to NMT 0.3% of reducing sugars, on the anhydrous basis, as Glucose.

5 SPECIFIC TESTS

Delete the following:

PH 〈791〉: 5.0–7.5, in a 14% (w/w) solution of Sorbitol Solution in carbon dioxide-free water (USP 1-May-2021)

Add the following:

CONDUCTIVITY

Sample: Sorbitol Solution

Analysis: Calibrate the conductivity meter using a 10 µS/cm certified reference standard. Measure the undiluted Sample while gently stirring with a magnetic stirrer.

Acceptance criteria: NMT 10 µS/cm (USP 1-May-2021)

WATER DETERMINATION 〈921〉 , Method I: 28.5%–31.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers. No storage requirements are specified.

USP REFERENCE STANDARDS 〈11〉

USP Diethylene Glycol RS USP Ethylene Glycol RS USP Sorbitol RS