Sodium Nitrite

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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NaNO₂ 68.99 (USP 1-Aug-2023)

Nitrous acid, sodium salt;

Sodium nitrite CAS RN®: 7632-00-0; UNII: M0KG633D4F.

1 DEFINITION

Sodium Nitrite contains NLT 98.0% and NMT 102.0% of sodium nitrite (NaNO₂ ), calculated on the dried basis.

2 IDENTIFICATION

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

B. Identification Tests—General 〈191〉, Chemical Identification Tests, Nitrite: Meets the requirements

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C. The retention time of the nitrite (USP 1-Aug-2023) peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

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3.1 Procedure

[Note—Use water with a resistivity of NLT 18 megohm-cm to prepare the solutions.] (USP 1-Aug-2023)

Mobile phase: 2.7 mM sodium carbonate and 0.3 mM sodium bicarbonate in water

Standard solution: 0.12 mg/mL of USP Sodium Nitrite RSand 1 μg/mL of USP Sodium Nitrate RS (USP 1-Aug-2023) in water

Sample solution: 0.12 mg/mL of Sodium Nitrite in water

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Conductivity with suppression

Columns

Guard: 4-mm × 50-mm, 13-μm (USP 1-Aug-2023) packing L110 (USP 1-Aug-2023)

Analytical: 4-mm × 200-mm; 9-μm packing L105

Flow rate: 1.5 mL/min

Injection volume: 25 μL

Run time: NLT 4 times the retention time of nitrite

3.3 System suitability

Sample: Standard solution

[Note—The relative retention times for nitrite and nitrate (USP 1-Aug-2023) ions are 1.0 and 1.85, respectively.]

3.4 Suitability requirements

Tailing factor: NMT 2.0 for nitrite (USP 1-Aug-2023)

Relative standard deviation: NMT 1.5% for nitrite (USP 1-Aug-2023)

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of sodium nitrite (NaNO₂ ) in the portion of Sodium Nitrite taken:

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

r_U = peak response of nitrite (USP 1-Aug-2023) from the Sample solution

r_S = peak response of nitrite (USP 1-Aug-2023) from the Standard solution

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

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

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

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Limit of Aluminum, Iron, and Selenium

[Note—Use water with a resistivity of NLT 18 megohm-cm to prepare the solutions.] (USP 1-Aug-2023)

Internal standard stock solution: To 2 mL each of commercially available 1 mg/mL scandium (for aluminum) and yttrium (for iron) and 10 mg/mL germanium (for selenium) standards in a 100-mL volumetric flask, add 2 mL of nitric acid and dilute with water to volume.

Internal standard solution: To 0.5 mL of the Internal standard stock solution in a 10-mL volumetric flask, add 0.5 mL of nitric acid and dilute with water to volume.

Blank solution: Dilute with water to volume, 0.125 mL of the Internal standard solution, 0.5 mL of nitric acid, and 0.5 mL of 80 ppm gold solution in a 50-mL volumetric flask.

Standard solutions: 2, 5, 50, and 100 ppb solutions for aluminum and selenium; 0, 50, 100, 500, and 1000 ppb for iron as follows. To suitable amounts of commercially available aluminum, Selenium, and iron standard solutions in a 50-mL volumetric flask, add 0.125 mL of the Internal standard solution, 0.5 mL of nitric acid, and 0.5 mL of 80 ppm gold solution, and dilute with water to volume.

Sample solution: To 1 g of Sodium Nitrite in a 50-mL volumetric flask, add 0.125 mL of the Internal standard solution, 2.5 mL of nitric acid, and 0.5 mL of 80 ppm gold solution, and dilute with water to volume.

Instrumental conditions

(See Plasma Spectrochemistry 〈730〉.)

Mode: Inductively coupled plasma–mass spectrometer (ICP–MS)

Spectrometer: Quadrupole mass spectrometer

Detector: Ion detector

System suitability

Sample: Standard solutions

Suitability requirements: Before analyzing samples, the instrument must pass a suitable performance check. Generate the calibration curve using the corresponding Standard solutions for each element under test. The linear regression coeficient is NLT 0.999.

Analysis

Sample: Sample solution

Determine the concentration of each element in the Sample solution using the calibration curve.

Calculate the amount of each element in the portion of Sodium Nitrite taken:

Result = [(C_t × V)/W]

C_t = concentration of each element in the Sample solution determined from the calibration curve (μg/mL or ppm)

V = volume of the Sample solution, 50 mL

W = weight of Sodium Nitrite taken (g) (USP 1-Aug-2023)

Acceptance criteria: See Table 1.

Table 1

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Limit of Sodium Nitrate

[Note—Use water with a resistivity of NLT 18 megohm-cm to prepare the solutions.] (USP 1-Aug-2023)

Mobile phase, Standard solution, (USP 1-Aug-2023) Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability

(USP 1-Aug-2023)

Sample: Standard solution

[Note—The relative retention times for nitrite and nitrate are 1.0 and about 1.85, respectively.]

Suitability requirements

Tailing factor: NMT 2.0 for nitrite (USP 1-Aug-2023)

Relative standard deviation: NMT 1.5% for nitrite and NMT 5% for nitrate (USP 1-Aug-2023)

Analysis

Sample: Sample solution

Calculate the percentage of sodium nitrate (NaNO₂ ) in the portion of Sodium Nitrite (USP 1-Aug-2023) taken:

Result = (r_U /r_S ) × (1/F) × 100

r_U = peak response of nitrate from the Sample solution

r_S = peak response of nitrite from the Sample solution

F = relative response factor for nitrate, 0.7

Acceptance criteria: NMT 0.4%

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Limit of Calcium and Potassium

[Note—Use water with a resistivity of NLT 18 megohm-cm to prepare the solutions.] (USP 1-Aug-2023)

Internal standard solution: 40 ppm scandium solution prepared from a suitable commercially available 1000 ppm high purity scandium standard solution in water

Blank solution: To 0.5 mL of the Internal standard solution in a 50-mL volumetric flask, add 0.5 mL of nitric acid and dilute with water to volume.

Standard solutions: 2.5, 5.0, 7.5, and 10.0 ppm of calcium and potassium prepared as follows. To suitable amounts of the respective commercially available calcium and potassium standard solutions in a suitable volumetric flask, add 0.5 mL of the Internal standard solution and 0.5 mL of nitric acid, and dilute with water to 50 mL.

Sample solution: To 1 g of Sodium Nitrite in a 50-mL volumetric flask, add 0.5 mL of the Internal standard solution and 2.5 mL of nitric acid, and dilute with water to volume.

Instrumental conditions

(See Plasma Spectrochemistry 〈730〉.)

Mode: Inductively coupled plasma–mass spectrometer (ICP–MS)

Spectrometer: Quadrupole mass spectrometer

Detector: Ion detector

System suitability

Sample: Standard solutions

Suitability requirements: Before analyzing samples, the instrument must pass a suitable performance check. Generate the calibration curve using the Standard solutions of the corresponding elements. The linear regression coeficient is NLT 0.999.

Analysis

Sample: Sample solution

Determine the concentration of each element in the Sample solution using the calibration curve.

Calculate the amount of each element in the portion of Sodium Nitrite taken:

Result = [(C_t × V)/W]

C_t = concentration of each element in the Sample solution determined from the calibration curve (ppm or μg/mL)

V = volume of the Sample solution, 50 mL

W = weight of Sodium Nitrite taken (g)

(USP 1-Aug-2023)

Acceptance criteria: See Table 2.

Table 2

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Limit of Carbonate

All carbonate solutions must be prepared fresh and stored in tightly sealed vials and stored in a cool area away from excessive heat.

Standard stock solution: 1 mg/mL of carbonate prepared as follows. Dissolve 0.177 g of USP Sodium Carbonate Anhydrous RS (USP 1-Aug- 2023) in a 100-mL volumetric flask, and dilute with water to volume.

Standard solutions: 0.50, 1.0, 2.0, 4.0, and 5.0 μg/mL carbonate in water from the Standard stock solution

Sample solution: Transfer 1.0 g of Sodium Nitrite into a 100-mL volumetric flask, and dilute with water to volume.

Instrumental conditions

(See Total Organic Carbon 〈643〉.) (USP 1-Aug-2023)

System suitability: Before analyzing samples, the total organic carbon (TOC) analyzer must pass a suitable performance check. Generate the calibration curve using the Standard solutions. The linear regression coeficient is NLT 0.995; the relative standard deviation for each

Standard solution is NMT 10%.

Analysis

Sample: Sample solution

Calculate the percentage of carbonate in the portion of Sodium Nitrite (USP 1-Aug-2023) taken:

Result = [(C_t × V (USP 1-Aug-2023) )/W] × 100

C_t = concentration of carbonate in the Sample solution determined from the calibration curve (USP 1-Aug-2023) (g/mL)

V = volume of the Sample solution, 100 mL (USP 1-Aug-2023)

W = weight of Sodium Nitrite (USP 1-Aug-2023) taken (g)

Acceptance criteria: NMT 0.02%

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Total Non-Purgeable Organic Content

Standard stock solution: Equivalent to 250 μg/mL of total organic carbon prepared as follows. Weigh 9 mg of USP Sucrose RS in a suitable flask, and add 15 mL of water.

Standard solutions: Equivalent to (USP 1-Aug-2023) 0.5, 2.0, and 10 μg/mL of total organic carbon in water from the Standard stock solution

Sample solution: Dissolve and dilute with water to volume, 5.0 g of Sodium Nitrite in a 100-mL volumetric flask.

Instrumental conditions

(See Total Organic Carbon 〈643〉.) (USP 1-Aug-2023)

System suitability: Before analyzing samples, the total organic carbon analyzer instrument must pass a suitable performance check.

Generate the calibration curve using the Standard solutions. The linear regression coeficient is NLT 0.99; relative standard deviation for the 2 μg/mLand 10 μg/mL calibration standards is NMT 15%.

Analysis

Sample: Sample solution

Calculate the amount, in ppm, of non-purgeable organic content present in the Sodium Nitrite (USP 1-Aug-2023) taken:

Result = [(C_t × V (USP 1-Aug-2023) )/W]

C_t = amount of non-purgeable organic content as determined from the calibration curve (μg/mL)

V = volume of the Sample solution, 100 mL (USP 1-Aug-2023)

W = weight of Sodium Nitrite (USP 1-Aug-2023) taken (g)

Acceptance criteria: NMT 10 ppm

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Limit of Sulfate

Standard solution: 0.0148 mg/mL of USP Sodium Sulfate Anhydrous RS (USP 1-Aug-2023) in water

Sample solution: 100 mg/mL of Sodium Nitrite in water

Analysis

Samples: Standard solution and (USP 1-Aug-2023) Sample solution

Evaporate 5 mL of the Standard solution or (USP 1-Aug-2023) Sample solution to dryness. Add 1 mL of dilute hydrochloric acid (prepared by adding 1 mL of hydrochloric acid to 19 mL of water). Pass through a prewashed small fIlter paper, and wash with two 2-mL portions of water. Dilute to 10 mL, and add 1 mL of barium chloride TS. Compare turbidity in the Standard solution and Sample solution, 10 min after adding the barium chloride TS.

Acceptance criteria: Any turbidity in the Sample solution should not exceed the turbidity in the Standard solution (NMT 0.01%).

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Limit of Chloride

Standard solution: 0.0165 mg/mL of USP Sodium Chloride RS (USP 1-Aug-2023) in water

Sample solution: 100 mg/mL of Sodium Nitrite in water

Analysis

Samples: Standard solution and Sample solution

To 2.0 mL of the Sample solution in a suitable test tube add 10 mL of water and 1 mL of glacial acetic acid and boil for 5 min. Pass through a chlorine-free fIlter paper, and dilute with water to 20 mL. Dilute 1 mL of the Standard solution with water to 20 mL in a separate test tube. Add 1 mL of nitric acid and 1 mL of 0.1 N silver nitrate. Allow to stand for 5 min protected from light and compare using a black background.

Acceptance criteria: Any turbidity in the Sample solution should not exceed the turbidity in the Standard solution (NMT 50 ppm).

5 SPECIFIC TESTS

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Bacterial Endotoxins Test 〈85〉: Meets the requirements (USP 1-Aug-2023)

Microbial Enumeration Tests 〈61〉: NMT 100 cfu/g, total aerobic microbial count and NMT 20 cfu/g, total yeasts and molds

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pH 〈791〉

Sample solution: 10% of Sodium Nitrite in water at 25° (USP 1-Aug-2023)

Acceptance criteria: 7.0–9.0

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Insoluble Matter

Sample solution: Dissolve 20 g (USP 1-Aug-2023) of Sodium Nitrite in 200 mL of (USP 1-Aug-2023) water.

Analysis: Heat the Sample solution to boiling in a covered beaker at about 100° for 1 h. Pass the hot solution through a suitable crucible fIlter of 10–15 μm pore size. Wash the beaker and fIlter with hot water, dry at 105°, cool in a desiccator, and weigh the residue.

Acceptance criteria: NMT 1 mg (0.005%) (USP 1-Aug-2023)

Loss on Drying 〈731〉

Analysis: Dry over silica gel for 4 h.

Acceptance criteria: NMT 0.25%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers and store at 25°, excursions permitted between 15° and 30°.

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USP Reference Standards 〈11〉

USP Sodium Carbonate Anhydrous RS

USP Sodium Chloride RS

USP Sodium Nitrate RS (USP 1-Aug-2023)

USP Sodium Nitrite RS

USP Sodium Sulfate Anhydrous RS (USP 1-Aug-2023)

USP Sucrose RS