Sucralose

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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C₁₂H₁₉CI₃O₈             397.63

1,6-Dichloro-1,6-dideoxy-ẞ-D-fructofuranosyl-4-chloro-4-deoxy-α-o-galactopyranoside;

1',4,6'-Trichlorogalactosucrose        CAS RN^®: 56038-13-2.

1 DEFINITION

Sucralose contains NLT 98.0% and NMT 102.0% of sucralose (C₁₂H₁₉CI₃O₈), calculated on the anhydrous basis. 

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

B. The retention time of the principal peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C. The R_F value of the principal spot of the Sample solution corresponds to that of Standard solution A, as obtained in the test for Related Compounds.

3 ASSAY

Change to read:

PROCEDURE

Mobile phase: Acetonitrile and water (3:17)

Chromatographic system

Mode: LC

Detector: Refractive index

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[NOTE-The retention time of sucralose is about 9 min.]

Suitability requirements

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution Calculate the percentage of sucralose (C₁₂H₁₉CI₃O₈) in the portion of Sucralose taken:

                     Result = (r_U/r_S) (C_S/C_U) × 100

r_U = peak response of sucralose from the Sample solution

r_S = peak response of sucralose from the Standard solution

C_S = concentration of USP Sucralose RS in the Standard solution (mg/mL) 

C_U = concentration of Sucralose in the Sample solution (mg/mL) 

Acceptance criteria: 98.0%-102.0% on the anhydrous basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.7%

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4.2 LIMIT OF METHANOL

^▲Standard stock solution: 1000 µg/mL of methanol in water

Standard solution: Transfer 1.000 g of Sucralose to a 22-mL headspace vial. Add 4.0 mL of 10% (w/v) sodium chloride solution. Add 1.00 mL of the Standard stock solution. Crimp a cap with a Teflon seal tightly onto the vial, and mix the solution well.

Sample solution: Add 1.000 g of Sucralose to a 22-ml. headspace vial. Add 4.0 mL of a 10% (w/v) sodium chloride solution. Add 1.00 mL of water. Crimp a cap with a Teflon seal tightly onto the vial, and mix the solution well.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: GC with balanced-pressure headspace sampler

Detector: Flame ionization

Column: 0.32 - mm x 30 - m 1.0-µm layer of phase G16

Temperatures

Injection port: 110°

Detector: 250°

Column: See Table 1.

Table 1

Carrier gas: Helium

Headspace sampler

[NOTE-The capillary column is installed through the GC inlet and through the transfer line to give on-column injection.]

Temperatures

Equilibration: 90°

Needle: 100°

Transfer line: 110°

Times

Equilibration: 10 min

Pressurization: 3.0 min

Withdrawal: 0.5 min

Injection: 0.15 min

Cycle: 25 min

Sampler delivery system: Helium set at 90 psi (not to exceed 100 psi)

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 10.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of methanol in the portion of Sucralose taken:

                     Result = (r_U x W_S)/[(r_S - r_U) x W_U x 100

r_U = peak area of methanol from the Sample solution

W_S = weight of methanol in the Standard solution (g)

r_S = peak area of methanol from the Standard solution

W_U = weight of Sucralose to prepare the Sample solution (g)

▲(NF 1-Dec-2023).

Acceptance criteria: NMT 0.1%

4.3 RELATED COMPOUNDS

Adsorbent: 0.20-mm layer of octadecylsilanized chromatographic silica gel. The thin-layer chromatographic plate also has a preadsorbent zone.

Detection reagent: Sulfuric acid in methanol (3 in 20)

Standard solution A: 10.0 mg/mL of USP Sucralose RS in methanol

Standard solution B: 0.5 mL of Standard solution A diluted with methanol to 10.0 mL

Sample solution: 100.0 mg/mL of Sucralose in methanol

Developing solvent system: Acetonitrile and sodium chloride solution (1 in 20) (3:7)

Application volume: 5 µL

Analysis

Samples: Standard solution A, Standard solution B, and Sample solution

Proceed as directed under Chromatography (621). Thin-Layer Chromatography. Spray the plate with Detection reagent. Heat the plate for 10 min at 125°.

Acceptance criteria: The R_F value of the principal spot from the Sample solution corresponds to that obtained from Standard solution A, and the color of any other single spot from the Sample solution is not more intense than that of the principal spot from Standard solution B (0.5%).

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4.4 LIMIT OF HYDROLYSIS PRODUCTS

[NOTE-This test does not require a developing solvent.]

Adsorbent: 0.25-mm layer of chromatographic silica gel

Spray reagent: 12.3 mg/mL of p-anisidine and 16.6 mg/mL of phthalic acid in methanol. Store the solution in the dark and refrigerate to prevent discoloration. Discard if the solution becomes discolored. [CAUTION-P-Anisidine is toxic if inhaled or if absorbed through the skin.]

Standard solution A: 100 mg/mL of mannitol

Standard solution B: 0.4 mg/mL of Fructose and 100 mg/mL of mannitol

Sample solution: 250 mg/mL of Sucralose in methanol

Application volume: 5-µL portions separately applied in 1-µL increments, allowing the plate to dry between applications

Analysis

Samples: ^▲Standard solution A, Standard solution B. _{▲(NF 1-Dec-2023)} and Sample solution

Proceed as directed under Chromatography (621) Thin-Layer Chromatograpby. Spray the plate with Spray reagent, and heat the plate at 100 ±2° for 15 min. If the spot from Standard solution A has darkened, repeat the test, heating for a shorter period of time. Immediately after heating, view the plate against a dark background.

Acceptance criteria: The color of the spot from the Sample solution is not more intense than that from Standard solution B (0.1%).

5 SPECIFIC TESTS

Change to read:

5.1 OPTICAL ROTATION (781S), Procedures, Specific Rotation

Sample solution: 10 mg/mL of Sucralose^▲, calculated on the anhydrous basis _{▲(NF 1-Dec-2023)}

Acceptance criteria: +84.0° to +87.5° at 20°

5.2 WATER DETERMINATION (921), Method /

NMT 2.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers, in a cool, dry place, at a temperature not exceeding 21".

USP REFERENCE STANDARDS (11)

USP Sucralose RS