Sodium Nitrite Injection

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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1 DEFINITION

Sodium Nitrite Injection is a sterile solution of Sodium Nitrite in Water for Injection. It contains NLT 95.0% and NMT 105.0% of the labeled amount of sodium nitrite (NaNO₂ ).

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: Nominally 0.12 mg/mL of sodium nitrite in water from a suitable volume of Injection

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: Ion chromatography

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 2.0% for nitrite (USP 1-Aug-2023)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of sodium nitrite (NaNO₂ ) in the portion of Injection 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 = nominal concentration of sodium nitrite in the Sample solution (mg/mL)

Acceptance criteria: 95.0%–105.0%

4 IMPURITIES

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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.

4.1 System suitability

Sample: Standard solution

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

4.2 Suitability requirements

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

Relative standard deviation: NMT 2.0% for nitrite and NMT 5% for nitrate (USP 1-Aug-2023)

4.3 Analysis

Samples: Sample solution

Calculate the percentage of sodium nitrate (NaNO₂ ) in the portion of Injection 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 of sodium nitrate, 0.7

Acceptance criteria: NMT 0.5%

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Limit of Nitrogen Oxide (NO_x ) Related Impurities

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

Blank solution 1: 0.1 N potassium chloride prepared as follows. Dissolve 7.46 g of potassium chloride in 1 L of water.

Blank solution 2: Acidified 0.1 N potassium chloride prepared as follows. In a 500-mL volumetric flask pipet 15-mL of 1 N hydrochloric acid and dilute with 0.1 N potassium chloride to volume.

Standard solution: 4.920 mg/mL of USP Sodium Nitrite RS (USP 1-Aug-2023) in water equivalent to 1000 μg/mL of nitrogen oxide (NO )

(USP 1-Aug-2023)

Sample solution: Dilute 10.0 mL of Injection with water to 50.0 mL. Store between 2° and 8°. Use 40 mL for each measurement.

4.4 System suitability

[Note—Under acidic conditions of pH less than 1.8, the nitrite is converted to equivalent amounts of nitrogen oxides with different oxidation states.]

Samples: Blank solution 2 and Standard solution

Suitability requirements: Generate a calibration curve of the mV readings for Blank solution 2, and a sequential addition of 100 μL, 100 μL, 800 μL, and 9 mL of the Standard solution to Blank solution 2 versus the log of the concentrations of the nitrogen oxide (NO ) in the solution. Use a pH meter equipped with a suitable nitrogen oxide (NO ) electrode to obtain the mV readings. Perform a linear regression without the zero concentration point and determine the slope and correlation coefficient (R). The slope must be between 54 and 60 mV and the linear regression coefficient is NLT 0.995.

4.5 Analysis

Samples: Blank solution 1, Blank solution 2, Standard solution, and Sample solution

Analyze the samples in the following order and obtain the pH meter readings in mV for 40-mL portions each of Blank solution 1 in duplicate, Sample solution in duplicate, and Blank solution 1; and 100-mL portions each of Blank solution 2, and Blank solution 2 plus 100 μL of Standard solution. [Note—This solution contains 1 μg/mL of nitrogen oxide (NO ).] Repeat the measurements.

Acceptance criteria: The mV reading obtained for the Sample solution is NMT the mV reading obtained for Blank solution 2 with 100 μL of the

Standard solution (NMT 1 ppm).

5 SPECIFIC TESTS

pH 〈791〉: 7.0–9.0

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

Other Requirements: Meets the requirements in Injections and Implanted Drug Products 〈1〉

6 ADDITIONAL REQUIREMENTS

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Packaging and Storage: Preserve preferably (USP 1-Aug-2023) in single-dose containers of Type I glass. Protect from direct light. Do not freeze.

Store at controlled room temperature.

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USP Reference Standards 〈11〉

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

USP Sodium Nitrite RS