Sodium Chloride

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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Portions of this monograph that are national USP text, and are not part of the harmonized text, are marked with symbols to specify this fact.

1 DEFINITION

Sodium Chloride contains NLT 99.0% and NMT 100.5% of sodium chloride (NaCl), calculated on the dried basis.

2 IDENTIFICATION

A. Identification Tests—General 〈191〉, Sodium: Meets the requirements

B. Chloride

Sample solution: 3 mg of Sodium Chloride in 2 mL of water

Analysis: Acidify the Sample solution with diluted nitric acid, and add 0.4 mL of silver nitrate TS. Shake, and allow to stand. A curdled, white precipitate is formed. Centrifuge, wash the precipitate with three 1-mL portions of water, and discard the washings. Carry out this operation rapidly in subdued light, disregarding the fact that the supernatant may not become perfectly clear. Suspend the precipitate in 2 mL of water, and add 1.5 mL of 10 N ammonium hydroxide.

Acceptance criteria: The precipitate dissolves easily with the possible exception of a few large particles, which dissolve more slowly.

3 ASSAY

Procedure

Sample: 50 mg of Sodium Chloride

Analysis: Dissolve the Sample in 50 mL of water, and titrate with 0.1 N silver nitrate VS (see Titrimetry 〈541〉), determining the endpoint

potentiometrically. Each mL of 0.1 N silver nitrate is equivalent to 5.844 mg of sodium chloride (NaCl).

Acceptance criteria: 99.0%–100.5% on the dried basis

4 IMPURITIES

Aluminum (where it is labeled as intended for use in the manufacture of peritoneal dialysis solutions, hemodialysis solutions, or hemofiltration solutions)

Buffer: Dissolve 50 g of ammonium acetate in 150 mL of water, adjust with glacial acetic acid to a pH of 6.0, and dilute with water to 250 mL.

Aluminum standard solution: To 352 mg of aluminum potassium sulfate in a 100-mL volumetric flask add a few mL of water, and swirl to dissolve. Add 20 mL of diluted sulfuric acid, dilute with water to volume, and mix. Immediately before use, transfer 1.0 mL of this solution to a 100-mL volumetric flask, and dilute with water to volume.

Sample solution: Dissolve 20.0 g of Sodium Chloride in 100 mL of water, and add 10 mL of Buffer. Extract this solution with successive portions of 20, 20, and 10 mL of a 0.5% solution of 8-hydroxyquinoline in chloroform, combining the chloroform extracts in a 50-mL volumetric flask. Dilute the combined extracts with chloroform to volume.

Standard solution: Prepare a mixture of 2.0 mL of Aluminum standard solution, 10.0 mL of Buffer, and 98 mL of water. Extract this mixture as described for the Sample solution, and dilute the combined extracts with chloroform to volume.

Blank solution: Prepare a mixture of 10 mL of Buffer and 100 mL of water. Extract this mixture as described for Sample solution, and dilute the combined extracts with chloroform to volume.

Instrumental conditions

(See Fluorescence Spectroscopy 〈853〉.)

Mode: Fluorescence

Excitation wavelength: 392 nm

Emission wavelength: 518 nm

Analysis

Samples: Sample solution, Standard solution, and Blank solution. Use the Blank solution to set the instrument to zero.

Determine the fluorescence intensities of the Sample solution and Standard solution.

Acceptance criteria: The fluorescence of the Sample solution does not exceed that of the Standard solution (0.2 ppm).

Change to read:

Arsenic 〈211〉, Procedures, Procedure 1 (CN 1-Jun-2023) : NMT 1 ppm

Barium

Analysis: To 5 mL of the solution prepared for the test for Appearance of Solution add 2 mL of 2 N sulfuric acid and 5 mL of water, as test solution. To another 5 mL of the solution prepared for the test for Appearance of Solution add 7 mL of water, as reference solution. Let stand for 2 h.

Acceptance criteria: Any opalescence in the test solution is not more intense than that in the reference solution.

Ferrocyanides

Sample solution: Dissolve 2.0 g in 6 mL of water.

Analysis: To the Sample solution add 0.5 mL of a mixture of 5 mL of ferric ammonium sulfate solution (10 mg/mL in 2.5 g/L (0.05 N) of sulfuric acid) and 95 mL of ferrous sulfate solution (10 mg/mL in water).

Acceptance criteria: No blue color develops in 10 min.

Iodides

Sample: 5 g of Sodium Chloride

Analysis: Moisten the Sample by the dropwise addition of a freshly prepared mixture of 0.15 mL of sodium nitrite solution (100 mg/mL), 2 mL of 1 N sulfuric acid, 25 mL of iodide-free starch TS, and 25 mL of water. After 5 min, examine the substance in natural light.

Acceptance criteria: No blue color is observed.

Change to read:

Iron

Sample solution: Use a 10-mL portion of the solution prepared for the test for Appearance of Solution.

Standard solution: Immediately before use, dilute Standard Iron Solution (see Iron 〈241〉, Procedures, Procedure 1 (CN 1-Jun-2023) ) 1 to 10 with water. This solution contains the equivalent of 1 μg/mL of iron. Combine 4 mL of this solution and 6 mL of water.

Analysis: To each of the solutions add 2 mL of a 200-mg/mL solution of citric acid and 0.1 mL of thioglycolic acid. Mix, make alkaline with stronger ammonia water, and dilute with water to 20 mL.

Acceptance criteria: After 5 min, any pink color in the Sample solution is not more intense than that from the Standard solution (NMT 2 ppm).

Limit of Bromides

[Note—Prepare the Sample solution and the Standard solution concomitantly.]

Standard solution: To 5.0 mL of a solution containing 3 μg/mL of potassium bromide add 2.0 mL of pH 4.7 phenol red TS and 1.0 mL of chloramine T solution (0.1 mg/mL), and mix immediately. After 2 min, add 0.15 mL of 0.1 N sodium thiosulfate, mix, and dilute with water to 10.0 mL.

Sample solution: To 0.5 mL of the solution prepared for the test for Appearance of Solution add 4.0 mL of water, 2.0 mL of pH 4.7 phenol red TS, and 1.0 mL of chloramine T solution (0.1 mg/mL), and mix immediately. After 2 min, add 0.15 mL of 0.1 N sodium thiosulfate, mix, and dilute with water to 10.0 mL.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV-Vis

Analytical wavelength: 590 nm

Comparison liquid: Water

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: The absorbance of the Sample solution is not greater than that of the Standard solution (NMT 100 ppm).

Limit of Phosphates

Sulfomolybdic acid solution: Dissolve with heating 2.5 g of ammonium molybdate in 20 mL of water. Dilute 28 mL of sulfuric acid in 50 mL of water, then cool. Mix the two solutions, and dilute with water to 100 mL.

Phosphate standard stock solution: 0.716 mg/mL of monobasic potassium phosphate in water

Phosphate standard solution: 7.16 μg/mL from Phosphate standard stock solution in water. [Note—Prepare this solution fresh.]

Standard solution: Dilute 2 mL of the Phosphate standard solution with water to 100 mL.

Sample solution: Dilute 2 mL of the solution prepared in the test for Appearance of Solution with water to 100 mL.

Analysis: To the Standard solution and the Sample solution add 4 mL of Sulfomolybdic acid solution, and add 0.1 mL of a mixture of 1 mL of stronger acid stannous chloride TS and 10 mL of 2 N hydrochloric acid. After 10 min, compare the colors of 20 mL of each solution.

Acceptance criteria: Any color in the Sample solution is not more intense than that in the Standard solution (NMT 25 ppm).

Limit of Potassium (where it is labeled as intended for use in the manufacture of injectable dosage forms, peritoneal dialysis solutions, hemodialysis solutions, or hemofiltration solutions)

[Note—The Standard solution and the Sample solution may be modified, if necessary, to obtain solutions of suitable concentrations adaptable to the linear or working range of the instrument.]

Standard solutions: Dissolve 1.144 g of potassium chloride, previously dried at 105° for 3 h, in water. Dilute with water to 1000 mL, and mix.

This solution contains the equivalent of 600 μg/mL of potassium. Dilute as required to obtain NLT 3 solutions at concentrations that span the expected value in the Sample solution.

Sample solution: Transfer 1.00 g of Sodium Chloride to a 100-mL volumetric flask. Add water and swirl to dissolve, dilute with water to volume, and mix.

Instrumental conditions

(See Atomic Absorption Spectroscopy 〈852〉.)

Mode: Atomic emission spectroscopy

Analytical wavelength: 766.5 nm

Flame: Air–acetylene

Analysis

Samples: Standard solutions and Sample solution

Measure, at least three times, the emission intensity of the Sample solution and the Standard solutions. Prepare a calibration curve from the mean of the readings obtained with the Standard solutions, and determine the concentration of potassium in the Sample solution.

Acceptance criteria: NMT 500 ppm

Magnesium and Alkaline-Earth Metals

Buffer: Prepare pH 10.0 ammonia–ammonium chloride buffer by dissolving 5.4 g of ammonium chloride in 20 mL of water, adding 20 mL of ammonium hydroxide, and diluting with water to 100 mL.

Analysis: To 200 mL of water add 0.1 g of hydroxylamine hydrochloride, 10 mL of Buffer, 1 mL of 0.1 M zinc sulfate, and 0.15 g of eriochrome black T trituration. Heat to 40°. Titrate this solution with 0.01 M edetate disodium VS until the violet color changes to deep blue. To this solution add 10.0 g of Sodium Chloride dissolved in 100 mL of water. If the color changes to violet, titrate the solution with 0.01 M edetate disodium VS to a deep blue endpoint.

Acceptance criteria: The volume of 0.01 M edetate disodium consumed in the second titration does not exceed 2.5 mL (NMT 100 ppm, calculated as Ca).

Nitrites

Sample solution: To 10 mL of the solution prepared in the test for Appearance of Solution add 10 mL of water.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV-Vis

Analytical wavelength: 354 nm

Cell: 1 cm

Analysis

Sample: Sample solution

Acceptance criteria: Absorbance is NMT 0.01.

Sulfate

[Note—All solutions used for this test must be prepared with distilled water.]

Sulfate standard solution A: To 181 mg of potassium sulfate in a 100-mL volumetric flask add a few mL of 30% alcohol. Swirl to dissolve, dilute with 30% alcohol to volume, and mix. Immediately before use, transfer 10.0 mL of this solution to a 1000-mL volumetric flask, and dilute with 30% alcohol to volume (10 μg/mL of sulfate).

Sulfate standard solution B: To 181 mg of potassium sulfate in a 100-mL volumetric flask add a few mL of water. Swirl to dissolve, dilute with water to volume, and mix. Immediately before use, transfer 10.0 mL of this solution to a 1000-mL volumetric flask, and dilute with water to volume (10 μg/mL of sulfate).

Sodium chloride solution: 50 mg/mL of Sodium Chloride in water

Barium chloride solution: 250 mg/mL of barium chloride in water

Standard solution: To 1.5 mL of Sulfate standard solution A add 1 mL of Barium chloride solution. Shake, and allow to stand for 1 min. To 2.5 mL of the resulting suspension add 15 mL of Sulfate standard solution B and 0.5 mL of 5 N acetic acid, and mix.

Sample solution: To 1.5 mL of Sulfate standard solution A add 1 mL of Barium chloride solution. Shake, and allow to stand for 1 min. To 2.5 mL of the resulting suspension add 15 mL of Sodium chloride solution and 0.5 mL of 5 N acetic acid, and mix.

Acceptance criteria: Any opalescence produced in the Sample solution after 5 min standing is NMT that produced in the Standard solution (200 ppm).

5 SPECIFIC TESTS

Appearance of Solution: Dissolve 20.0 g of Sodium Chloride in carbon dioxide-free water, and dilute with the same solvent to 100.0 mL. This solution is clear and colorless.

Acidity or Alkalinity

Analysis: To 20 mL of the solution prepared for the test for Appearance of Solution add 0.1 mL of bromothymol blue TS.

Acceptance criteria: NMT 0.5 mL of 0.01 N hydrochloric acid or 0.01 N sodium hydroxide is required to change the color of this solution.

Loss on Drying 〈731〉

Sample: 1.000 g

Analysis: Dry the Sample in an oven at 105° for 2 h.

Acceptance criteria: NMT 0.5%

Bacterial Endotoxins Test 〈85〉: The level of bacterial endotoxins is such that the requirement under the relevant dosage form monograph(s) in which Sodium Chloride is used can be met. Where the label states that Sodium Chloride must be subjected to further processing during the preparation of injectable dosage forms, the level of bacterial endotoxins is such that the requirement under the relevant dosage form monograph(s) in which Sodium Chloride is used can be met.

Sterility Tests 〈71〉: Where the label states that Sodium Chloride is sterile, it meets the requirements for Sterility under the relevant dosage form monograph(s) in which Sodium Chloride is used.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

Labeling: Where Sodium Chloride is intended for use in the manufacture of injectable dosage forms, peritoneal dialysis solutions, hemodialysis solutions, or hemo filtration solutions, it is so labeled. Where Sodium Chloride must be subjected to further processing during the preparation of injectable dosage forms to ensure acceptable levels of bacterial endotoxins, it is so labeled. Where Sodium Chloride is sterile, it is so labeled.