Ringer's 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

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Ringer’s Injection is a sterile solution of Sodium Chloride, Potassium Chloride, and Calcium Chloride in Water for Injection. It contains, in each 100 mL, NLT 323.0 mg and NMT 354.0 mg of sodium (Na) [equivalent to NLT 820.0 mg and NMT 900.0 mg of sodium chloride (NaCl)]; NLT 14.9 mg and NMT 16.5 mg of potassium (K) [equivalent to NLT 28.5 mg and NMT 31.5 mg of potassium chloride (KCl)]; NLT 8.20 mg and NMT 9.80 mg of calcium (Ca) [equivalent to NLT 30.0 mg and NMT 36.0 mg of calcium chloride (CaCl₂ · 2H₂O)]; and NLT 523.0 mg and NMT 580.0 mg of chloride (Cl) as sodium chloride (NaCl), potassium chloride (KCl), and calcium chloride (CaCl₂ · 2H₂O). It contains no antimicrobial agents.

[Note—The potassium, calcium, sodium ion, and chloride contents of Ringer’s Injection are approximately 4, 4.5, 147.5, and 156 mEq/L, respectively.]

(USP 1-Dec-2021)

2 IDENTIFICATION

A. Identification Tests—General 〈191〉, Chemical Identification Tests, Calcium and Chloride: Meets the requirements of test A for Calcium, and test A for Chloride

B. Sodium: A sample imparts an intense yellow color to a nonluminous flame.

C. Potassium: A sample imparts a violet color to a nonluminous flame. The presence of small quantities of sodium masks the color unless the yellow color produced by sodium is screened out by viewing through a blue filter that blocks the emission at 589 nm (sodium). It is transparent to emission at 404 nm (potassium).

[Note—Traditionally, cobalt glass has been used, but other suitable filters are commercially available.]

3 ASSAY

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3.1 Calcium

[Note—Concentrations of the Standard solutions and the Sample solution may be modified to fit the linear or working range of the atomic absorption spectrophotometer.]

Lanthanum chloride solution: Transfer 17.69 g of lanthanum chloride to a 200-mL volumetric flask, add 100 mL of water, and carefully add 50 mL of hydrochloric acid. Mix, and allow to cool. Dilute with water to volume.

Calcium stock solution: 1 mg/mL of calcium (Ca) prepared as follows. Transfer 499.5 mg of primary standard calcium carbonate to a 200-mL volumetric flask, and add 10 mL of water. Carefully add 5 mL of diluted hydrochloric acid, and swirl to dissolve the calcium carbonate. Dilute with water to volume.

Standard solutions: 0.010, 0.015, and 0.020 mg/mL of calcium (Ca) prepared as follows. To three separate 100-mL volumetric flasks, each containing 5.0 mL of Lanthanum chloride solution, add 1.0, 1.5, and 2.0 mL, respectively, of Calcium stock solution. Dilute the contents of each flask with water to volume.

Sample solution: Transfer 20.0 mL of Injection, equivalent to 1.8 mg of calcium (Ca), to a 100-mL volumetric flask containing 5.0 mL of Lanthanum chloride solution. Dilute with water to volume.

Blank: Transfer 5.0 mL of Lanthanum chloride solution to a 100-mL volumetric flask, and dilute with water to volume.

Instrumental conditions

(See Atomic Absorption Spectroscopy 〈852〉.)

Mode: Atomic absorption spectrophotometry

Analytical (USP 1-Dec-2021) wavelength: Calcium emission line, 422.7 nm

Lamp: Calcium hollow-cathode

Flame: Air–acetylene

Analysis

Samples: Standard solutions, Sample solution, and Blank

Plot the absorbances of the Standard solutions versus the concentration, in mg/mL, of calcium, and draw the straight line best fitting the three plotted points. From the graph, determine the concentration (C), in mg/mL, of calcium in the Sample solution.

Calculate the quantity, in mg, of calcium (Ca) in each 100 mL of Injection taken:

Result = C × D × F

C = concentration of calcium in the Sample solution, as determined from the graph (mg/mL)

D = dilution factor of the Sample solution, 5

F = conversion factor for each 100 mL of Injection, 100 mL

Acceptance criteria: 8.20–9.80 mg

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3.2 Potassium

Solution A: Suitable nonionic wetting agent (1 in 500)

Solution B: 10.93 mg/mL of sodium chloride in water

Standard stock solution: 100 µg/mL of potassium prepared as follows. Dissolve 190.7 mg of potassium chloride, previously dried at 105° for 2 h, in 50 mL of water. Transfer to a 1-L volumetric flask, and dilute with water to volume.

Standard solutions: 0.005, 0.01, 0.015, and 0.020 mg/mL of potassium prepared as follows. Transfer 10 mL of Solution B to each of four separate 100-mL volumetric flasks each containing 10.0 mL of Solution A. To each flask add 5.0, 10.0, 15.0, and 20.0 mL of Standard stock solution, respectively, and dilute with water to volume.

Sample solution: Transfer 10 mL of Injection to a 100-mL volumetric flask. Add 10.0 mL of Solution A. Dilute with water to volume.

Blank: Transfer 10 mL of Solution B to a 100-mL volumetric flask containing 10.0 mL of Solution A. Dilute with water to volume.

Instrumental conditions

Mode: Flame photometry (USP 1-Dec-2021)

Analytical (USP 1-Dec-2021) wavelength: Maximum transmittance at 766 nm

Analysis

Samples: Standard solutions, Sample solution, and Blank

Set the instrument for maximum transmittance and adjust to zero transmittance with the Blank. Adjust the instrument to 100% transmittance with the most concentrated of the Standard solutions. Read the percentage transmittance of the other Standard solutions, and plot transmittances versus concentration of potassium. Draw the straight line best fitting the four plotted points. From the graph, calculate the concentration of potassium in the Sample solution.

Calculate the quantity, in mg, of potassium (K) in each 100 mL of Injection taken:

Result = C × D × F

C = concentration of potassium in the Sample solution, as determined from the graph (mg/mL)

D = dilution factor of the Sample solution, 10

F = conversion factor for each 100 mL of Injection, 100 mL ▲ (USP 1-Dec-2021)

Acceptance criteria: 14.9–16.5 mg

Change to read:

3.3 Sodium

Solution A: Suitable nonionic wetting agent (1 in 500)

Standard stock solution: 100 µg/mL of sodium in water prepared as follows. Dissolve 254.2 mg of sodium chloride, previously dried at 105° for 2 h, in 50 mL of water. Transfer the resulting solution to a 1-L volumetric flask, and dilute with water to volume.

Standard solutions: 0.005, 0.010, 0.015, and 0.020 mg/mL of sodium prepared as follows. Transfer 10 mL of Solution A to each of four separate 100-mL volumetric flasks. To each flask add 5.0, 10.0, 15.0, and 20.0 mL of Standard stock solution, respectively, and dilute with water to volume.

Sample solution: Transfer 5 mL of Injection into a 1-L volumetric flask containing 100 mL of Solution A. Dilute with water to volume.

Blank: Transfer 10 mL of Solution A to a 100-mL volumetric flask. Dilute with water to volume.

Instrumental conditions

Mode: Flame photometry (USP 1-Dec-2021)

Analytical (USP 1-Dec-2021) wavelength: Maximum transmittance at 589 nm

Analysis

Samples: Standard solutions, Sample solution, and Blank

Set the instrument for maximum transmittance and adjust to zero transmittance with the Blank. Adjust the instrument to 100% transmittance with the most concentrated of the Standard solutions. Read the percentage transmittance of the other Standard solutions, and plot transmittances versus concentration of sodium. Draw the straight line best fitting the four plotted points. From the graph, calculate the concentration of sodium in the Sample solution.

Calculate the quantity, in mg, of sodium (Na) in each 100 mL of Injection:

Result = C × D × F

C = concentration of sodium in the Sample solution, as determined from the graph (mg/mL)

D = dilution factor of the Sample solution, 200

F = conversion factor for each 100 mL of Injection, 100 mL ▲ (USP 1-Dec-2021)

Acceptance criteria: 323.0–354.0 mg

Change to read:

3.4 Chloride

Sample solution: Transfer 10 mL of Injection into a conical flask. Add 10 mL of glacial acetic acid, 75 mL of methanol, and 3 drops of eosin Y TS.

Titrimetric system

Mode: Direct titration

Titrant: 0.1 N silver nitrate VS

Endpoint detection: Visual

Analysis

Sample: Sample solution

Titrate, with shaking, with Titrant to a pink endpoint.

Calculate the quantity, in mg, of chloride (Cl) in 100 mL of Injection:

Result = V × N_A × F_e × F_c

V = Titrant volume consumed by the Sample solution (mL)

N_A = actual normality of the Titrant (mEq/mL)

F_e = equivalency factor, 35.45 mg/mEq

F_c = conversion factor for each 100 mL of Injection, 10 (USP 1-Dec-2021)

Acceptance criteria: 523.0–580.0 mg

4 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: NMT 0.5 USP Endotoxin Units/mL

Add the following:

Sterility Tests 〈71〉: Meets the requirements (USP 1-Dec-2021)

pH 〈791〉: 5.0–7.5

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

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Package in single-dose glass or plastic containers. Glass containers are preferably of Type I or Type II glass.

Labeling: The label states the total osmolar concentration in mOsmol/L. Where the contents are less than 100 mL, the label alternatively may state the total osmolar concentration in mOsmol/mL.