Saccharin Calcium

(sak' a rin kal' see um).

C14H8CaN2O6S2·3½H2O467.48

C14H8CaN2O6S2404.44
1,2-Benzisothiazol-3(2H)-one, 1,1-dioxide, calcium salt, hydrate (2:7);
1,2-Benzisothiazolin-3-one 1,1-dioxide calcium salt hydrate (2:7)

[6381-91-5].
Anhydrous

[6485-34-3].

DEFINITION

Saccharin Calcium contains NLT 99.0% and NMT 101.0% of C14H8CaN2O6S2, calculated on the anhydrous basis.

IDENTIFICATION

• A. Infrared Absorption

197K

Sample: Dry at 105

to constant weight.

• B. Procedure

Sample solution: 100 mg/mL

Analysis: To the Sample solution add 2 drops of methyl red TS, and neutralize with 6 N ammonium hydroxide. Add 3 N hydrochloric acid, dropwise, until the solution is acid to the indicator. Add ammonium oxalate TS.

Acceptance criteria: A white precipitate is formed when the ammonium oxalate is added. This precipitate is insoluble in 6 N acetic acid but dissolves in hydrochloric acid.

• C. Calcium salts moistened with hydrochloric acid impart a transient yellowish-red color to a nonluminous flame.

ASSAY

• Procedure

Sample solution: 3 mg/mL of Saccharin Calcium in glacial acetic acid. [Note—Slight heating may be needed to dissolve the sample. ]

Analysis: Titrate Sample solution with 0.1 N perchloric acid, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary correction (see Titrimetry

541

). Each mL of 0.1 N perchloric acid is equivalent to 20.22 mg of C14H8CaN2O6S2.

Acceptance criteria: 99.0%–101.0% on the anhydrous basis

IMPURITIES

Inorganic Impurities

• Heavy Metals, Method I

231

Sample: 4 g in 46 mL

Analysis: Add 4 mL of dilute hydrochloric acid (1 in 12), mix, and rub the inner wall of the vessel with a glass rod until crystallization begins. Allow the solution to stand for 1 h, then pass through a dry filter, discarding the first 10 mL of the filtrate, and use 25 mL of the subsequent filtrate for the Sample preparation.

Acceptance criteria: NMT 10 ppm

Organic Impurities

• Procedure 1: Limit of Toluenesulfonamides

Internal standard solution: 0.25 mg/mL of caffeine in methylene chloride

Standard stock solution: 20.0 µg/mL of USP o-Toluenesulfonamide RS and 20.0 µg/mL of USP p-Toluenesulfonamide RS in methylene chloride

Standard solution: Evaporate 5.0 mL of Standard stock solution to dryness in a stream of nitrogen. Dissolve the residue in 1.0 mL of the Internal standard solution.

Sample stock solution: 200 mg/mL in water. If necessary, adjust with 1 N sodium hydroxide or 1 N hydrochloric acid to a pH of 7–8 before final dilution.

Sample solution: Shake 50 mL of the Sample stock solution with four quantities each of 50 mL of methylene chloride. Combine the lower layers, dry over anhydrous sodium sulfate, and filter. Wash the filter and the sodium sulfate with 10 mL of methylene chloride. Combine the solution and the washings, and evaporate almost to dryness in a water bath at a temperature not exceeding 40

. Using a small quantity of methylene chloride, quantitatively transfer the residue into a suitable 10-mL tube, evaporate to dryness in a stream of nitrogen, and dissolve the residue in 1.0 mL of the Internal standard solution.

Blank solution: Evaporate 200 mL of methylene chloride to dryness in a water bath at a temperature not exceeding 40

. Dissolve the residue in 1 mL of methylene chloride.

Chromatographic system

(See Chromatography

621

, System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.53-mm × 10-m fused silica column, coated with G3 phase (film thickness 2 µm)

Temperature

Injector: 250

Detector: 250

Column: 180

Carrier gas: Nitrogen

Flow rate: 10 mL/min

Injection size: 1 µL

Split ratio: 2:1

System suitability

Samples: Standard solution and Blank solution

[Note—The substances are eluted in the following order: o-toluenesulfonamide, p-toluenesulfonamide, and caffeine. ]

Suitability requirements: There are no peaks present in the Blank solution at the retention times of the Internal standard solution, o-toluenesulfonamide, and p-toluenesulfonamide, Blank solution.

Resolution: NLT 1.5 between o-toluenesulfonamide and p-toluenesulfonamide, Standard solution

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: If any peaks due to o-toluenesulfonamide and p-toluenesulfonamide appear in the chromatogram obtained with the Sample solution, the ratio of their areas to that of the Internal standard solution is NMT the corresponding ratio in the chromatogram obtained with the Standard solution.

Individual impurities: See Impurity Table 1.

Impurity Table 1

Name	Acceptance Criteria NMT (ppm)
o-Toluenesulfonamide	10
p-Toluenesulfonamide	10

• Procedure 2: Limit of Benzoate and Salicylate

Sample solution: 50 mg/mL

Analysis: To 10 mL of the Sample solution add 5 drops of 6 N acetic acid and 3 drops of ferric chloride TS.

Acceptance criteria: No precipitate or violet color appears.

SPECIFIC TESTS

• Water Determination, Method I

921

: NMT 15.0%

• Readily Carbonizable Substances

271

Sample solution: 40 mg/mL in sulfuric acid (94.5%–95.5% (w/w) of H2SO4), 48

–50

for 10 min

Acceptance criteria: The Sample solution has no more color than Matching Fluid A, when viewed against a white background.

• Clarity of Solution

[Note—The Sample solution is to be compared to Reference suspension A and to water in diffused daylight 5 min after preparation of Reference suspension A. ]

Diluent: 200 g/L solution of sodium acetate

Hydrazine solution: 10.0 mg/mL of hydrazine sulfate. [Note—Allow to stand for 4–6 h. ]

Methenamine solution: Transfer 2.5 g of methenamine to a 100-mL glass-stoppered flask, add 25.0 mL of water, insert the glass stopper, and mix to dissolve.

Primary opalescent suspension: Transfer 25.0 mL of Hydrazine solution to the Methenamine solution in the 100-mL glass-stoppered flask. Mix, and allow to stand for 24 h. [Note—This suspension is stable for 2 months, provided it is stored in a glass container free from surface defects. The suspension must not adhere to the glass and must be well mixed before use. ]

Opalescence standard: Transfer 15.0 mL of the Primary opalescent suspension and dilute to 1000 mL. [Note—This suspension should not be used beyond 24 h after preparation. ]

Reference suspension A: Opalescence standard and water (1 in 20)

Reference suspension B: Opalescence standard and water (1 in 10)

Sample solution: 200 mg/mL in Diluent

Analysis

Samples: Diluent, Reference suspension A, Reference suspension B, Sample solution, and water

Transfer a sufficient portion of Sample solution to a test tube of colorless, transparent, neutral glass with a flat base and an internal diameter of 15–25 mm to obtain a depth of 40 mm. Similarly transfer portions of Reference suspension A, Reference suspension B, water, and Diluent to separate matching test tubes. Compare solutions in diffused daylight, viewing vertically against a black background (see Spectrophotometry and Light-Scattering

851

, Visual Comparison). [Note—The diffusion of light must be such that Reference suspension A can readily be distinguished from water, and that Reference suspension B can readily be distinguished from Reference suspension A. ]

Acceptance criteria: The Sample solution shows the same clarity as that of water, or Diluent, or its opalescence is NMT that of Reference suspension A.

• Color of Solution

Diluent A: 200 g/L solution of sodium acetate

Diluent B: 10 g/L solution of hydrochloric acid

Standard stock solution: Ferric chloride CS, cobaltous chloride CS, cupric sulfate CS, and Diluent B (3.0:3.0:2.4:1.6)

Standard solution: Standard stock solution and Diluent B (1:99). [Note—Prepare the Standard solution immediately before use. ]

Sample solution: Use the Sample solution from Clarity of Solution.

Analysis

Samples: Diluent A, Standard solution, Sample solution, and water

Transfer a sufficient portion of the Sample solution to a test tube of colorless, transparent, neutral glass with a flat base and an internal diameter of 15–25 mm to obtain a depth of 40 mm. Similarly transfer portions of the Standard solution, Diluent A, and water to separate matching test tubes. Compare solutions in diffused daylight, viewing vertically against a white background (see Spectrophotometry and Light-Scattering

851

, Visual Comparison).

Acceptance criteria: The Sample solution has the appearance of water or Diluent A, or is not more intensely colored than the Standard solution.

ADDITIONAL REQUIREMENTS

• Packaging and Storage: Preserve in well-closed containers. Store at room temperature.

• Labeling: Where the quantity of saccharin calcium is indicated in the labeling of any preparation containing Saccharin Calcium, this shall be expressed in terms of saccharin (C7H5NO3S).

• USP Reference Standards

USP Saccharin Calcium RS

USP o-Toluenesulfonamide RS

C7H9NO2S 171.22

USP p-Toluenesulfonamide RS

C7H9NO2S 171.22

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
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org

USP35–NF30 Page 4596

Pharmacopeial Forum: Volume No. 32(4) Page 1114

Chromatographic Column—

SACCHARIN CALCIUM

Chromatographic columns text is not derived from, and not part of, USP 35 or NF 30.