Sodium Chloride
NaCl 58.44
Sodium Chloride
[7647-14-5].
(soe' dee um klor' ide).
NaCl 58.44
Sodium Chloride
[7647-14-5].DEFINITION
Sodium Chloride contains NLT 99.0% and NMT 100.5% of NaCl, calculated on the dried basis.
IDENTIFICATION
• A. Identification Tests—General, Sodium 
191
:
Meets the requirements
191:
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.
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 NaCl.
541), determining the endpoint potentiometrically. Each mL of 0.1 N silver nitrate is equivalent to 5.844 mg of NaCl.
Acceptance criteria:
99.0%–100.5% on the dried basis
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.
Standard aluminum 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.
Standard solution:
Prepare a mixture of 2.0 mL of Standard aluminum 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.
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.
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
Mode:
Fluorescence
Excitation wavelength:
392 nm
Emission wavelength:
518 nm
Analysis
Samples:
Standard solution, Sample 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).
• Arsenic, Method I 211:
NMT 1 ppm
211:
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. To another 5 mL of the solution prepared for the test for Appearance of Solution add 7 mL of water.
Acceptance criteria:
The solutions are equally clear after standing for 2 h.
• 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 0.1 N 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.
• 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) 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.
241) 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
Mode:
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
Phosphate stock standard solution:
0.716 mg/mL of monobasic potassium phosphate in water
Phosphate standard solution:
7.16 µg/mL from Phosphate stock standard 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.
Sulfomolybdic acid solution:
Dissolve with heating 2.5 g of ammonium molybdate in 20 mL of water. Dilute 28 mL of sulfuric acid with 50 mL of water, then cool. Mix the two solutions, and dilute 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.
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
Mode:
Atomic absorption spectrophotometry
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 to 100 mL with water.
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 0.2 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.
. 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
Mode:
UV-Vis
Analytical wavelength:
354 nm
Cell:
1 cm
Analysis
Sample:
Sample solution
Acceptance criteria:
Absorbance is NMT 0.01.
• Sulfate
Standard sulfate 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).
Standard sulfate 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 Standard sulfate 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 Standard sulfate solution B and 0.5 mL of 5 N acetic acid, and mix.
Sample solution:
To 1.5 mL of Standard sulfate 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 turbidity produced in the Sample solution after 5 min standing is NMT that produced in the Standard solution (200 ppm).
• Heavy Metals, Method I 231:
NMT 5 ppm
231:
NMT 5 ppm
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:
Dry 1.000 g at 105 for 2 h: it loses NMT 0.5% of its weight.
731:
Dry 1.000 g at 105 for 2 h: it loses NMT 0.5% of its weight.
• 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.
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.
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.
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 hemofiltration 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.
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 |
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 71 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
USP35–NF30 Page 4652
Pharmacopeial Forum: Volume No. 31(5) Page 1401