Lactated Ringer's Injection
If you find any inaccurate information, please let us know by providing your feedback here
Tóm tắt nội dung
This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition
Issued and maintained by the United States Pharmacopeial Convention (USP)
1 DEFINITION
Lactated Ringer's Injection is a sterile solution of Calcium Chloride, Potassium Chloride, Sodium Chloride, and Sodium Lactate in Water for Injection. It contains, in each 100 mL, NLT 285.0 and NMT 315.0 mg of sodium (Na) [as sodium chloride (NaCl) and sodium lactate (C3H5NaO3)], NLT 14.2 and NMT 17.3 mg of potassium (K) [equivalent to NLT 27.0 and NMT 33.0 mg of potassium chloride (KCl)], NLT 4.90 and NMT 6.00 mg of calcium (Ca) [equivalent to NLT 18.0 and NMT 22.0 mg of calcium chloride (CaCl2 · 2H2O)], NLT 368.0 and NMT 428.0 mg of chloride (Cl) [as sodium chloride (NaCl), potassium chloride (KCl), and calcium chloride (CaCl2 · 2H2O)], and NLT 231.0 and NMT 261.0 mg of lactate ((C3H5O3) [equivalent to NLT 290.0 and NMT 330.0 mg of sodium lactate (C3H5NaO3)]. It contains no antimicrobial agents.
[Note—The calcium, potassium, and sodium contents of Lactated Ringer's Injection are approximately 2.7, 4, and 130 mEq/L, respectively.]
2 IDENTIFICATION
Change to read:
A. Identification Tests—General 〈191〉: Meets the requirements of the (USP 1-May-2021) test
(USP 1-May-2021) under Chloride and test A under Calcium
B. Potassium: The sample imparts a violet color to a nonluminous flame. Because the presence of small quantities of sodium masks the color, screen out the yellow color produced by sodium by viewing through a blue filter that blocks the emission at 589 nm (sodium), but is transparent to emission at 404 nm (potassium). [Note—Traditionally, cobalt glass has been used, but other suitable filters are commercially available.]
C. Sodium: The sample imparts an intense yellow color to a nonluminous flame.
D. The retention time of the lactate peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay for Lactate.
3 ASSAY
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.]
Solution A: Transfer 17.69 g of lanthanum chloride to a 200-mL volumetric flask, add 100 mL of water, carefully add 50 mL of hydrochloric acid, and allow to cool. Dilute with water to volume.
Calcium stock solution: 1 mg/mL of calcium 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 dilute 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, prepared as follows. To three separate 100-mL volumetric flasks, each containing 5.0 mL of Solution A, 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: Dilute with water, 20.0 mL of Injection, equivalent to 1 mg of calcium, in a 100-mL volumetric flask containing 5.0 mL of Solution A to volume, and mix.
Blank: 5.0 mL of Solution A diluted with water to 100.0 mL
Instrumental conditions
(See Atomic Absorption Spectroscopy 〈852〉.)
Mode: Atomic absorption spectrophotometer
Analytical wavelength: Calcium emission line at 422.7 nm
Lamp: Calcium hollow-cathode
Flame: Air–acetylene
Analysis
Samples: Standard solutions, Sample solution, and Blank
Concomitantly determine the absorbances of the Standard solutions and the Sample solution. 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 this graph, calculate the concentration (C) in mg/mL, of calcium in the Sample solution.
Calculate the quantity of calcium in each 100 mL of Injection taken:
Result = C × D × F
C = concentration of calcium in the Sample solution (mg/mL)
D = dilution factor for the Sample solution, 5
F = conversion factor for each 100 mL of Injection, 100 mL
Acceptance criteria: 4.90–6.00 mg of calcium per 100 mL of Injection
3.2 Potassium
Solution A: Suitable nonionic wetting solution (1 in 500)
Solution B: 10.93 mg/mL of sodium chloride in water
Standard stock solution: 0.100 mg/mL of potassium, prepared as follows. Transfer 190.7 mg of potassium chloride, previously dried at 105° for 2 h, 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 potassium, prepared as follows. To four separate 100-mL volumetric flasks, each containing 10.0 mL of Solution A and 10 mL of Solution B, add 5.0, 10.0, 15.0, and 20.0 mL, respectively, of Standard stock solution.
Dilute the contents of each flask with water to volume.
Sample solution: Pipet 10 mL of Injection to a 100-mL volumetric flask containing 10 mL of Solution A, dilute with water to volume, and mix.
Blank: Transfer 10.0 mL of Solution A and 10 mL of Solution B to a 100-mL volumetric flask. Dilute with water to volume.
Instrumental conditions
Mode: Flame photometry
Analytical wavelength: Maximum transmittance at 766 nm
Analysis
Samples: Standard solutions, Sample solution, and Blank
Set the flame photometer for maximum transmittance. Adjust the instrument 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 of the Standard solutions versus the concentration, in mg/mL, of potassium. Draw the straight line best fitting the four plotted points. From this graph, calculate the concentration of potassium in the Sample solution.
Calculate the quantity, in milligrams, of potassium in each 100 mL of Injection taken:
Result = C × D × F
C = concentration of potassium in the Sample solution (mg/mL)
D = dilution factor for the Sample solution, 10
F = conversion factor for each 100 mL of Injection, 100 mL
Acceptance criteria: 14.2–17.3 mg of potassium per 100 mL of Injection
3.3 Sodium
Solution A: Suitable nonionic wetting solution (1 in 500)
Standard stock solution: 0.100 mg/mL of sodium, prepared as follows. Dissolve 254.2 mg of sodium chloride, previously dried at 105° for 2 h, in 50 mL of water. Transfer this 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. To four separate 100-mL volumetric flasks, each containing 10.0 mL of Solution A, add 5.0, 10.0, 15.0, and 20.0 mL, respectively, of Standard stock solution. Dilute the contents of each flask with water to volume.
Sample solution: Transfer 5 mL of Injection to a 1-L volumetric flask containing 100.0 mL of Solution A and dilute with water to volume.
Blank: Transfer 10.0 mL of Solution A to a 100-mL volumetric flask. Dilute with water to volume.
Instrumental conditions
Mode: Flame photometry
Analytical wavelength: Maximum transmittance at 589 nm
Analysis
Samples: Standard solutions, Sample solution, and Blank
Set the flame photometer for maximum transmittance. Adjust the instrument 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 of the Standard solutions versus concentration, in mg/mL, of sodium, and draw the straight line best fitting the four plotted points. From this graph, calculate the concentration of sodium in the Sample solution.
Calculate the quantity of sodium in each 100 mL of Injection taken:
Result = C × D × F
C = concentration of sodium in the Sample solution (mg/mL)
D = dilution factor for the Sample solution, 200
F = conversion factor for each 100 mL of Injection, 100 mL
Acceptance criteria: 285.0–315.0 mg of sodium per 100 mL of Injection
Change to read:
3.4 Chloride
Sample solution: Transfer 10 mL of Injection into a conical flask, and add 10 mL of glacial acetic acid and 75 mL of methanol.
Titrimetric system
(See Titrimetry 〈541〉.)
Mode: Direct titration
Titrant: 0.1 N silver nitrate VS
Endpoint detection: Visual
Analysis
Sample: Sample solution
Titrate the Sample solution, with shaking, with Titrant to a pink endpoint using 3 drops of eosin Y TS, as an indicator.
Calculate the labeled amount of chloride (Cl) in 100 mL of Injection taken:
Result = V × NA × Fe × Fc (USP 1-May-2021)
V = Titrant volume consumed by the Sample solution (mL)
NA (USP 1-May-2021) = actual normality of the Titrant (mEq/mL)
Fe (USP 1-May-2021) = equivalency factor, 35.45 mg/mEq
Fc = conversion factor for each 100 mL of Injection, 10 (USP 1-May-2021)
Acceptance criteria: 368.0–428.0 mg of chloride per 100 mL of Injection
3.5 Lactate
Mobile phase: Dicyclohexylamine, formic acid, and water (1:1:998)
System suitability solution: 3 mg/mL each of anhydrous sodium acetate and USP Sodium Lactate RS in water
Standard solution: 3 mg/mL of USP Sodium Lactate RS in water
Sample solution: Use undiluted Injection.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 210 nm
Column: 4.6-mm × 10-cm; packing L1
Flow rate: 1 mL/min
Injection volume: 20 μL
System suitability
Samples: System suitability solution and Standard solution
Suitability requirements
Resolution: NLT 2 between the acetate and lactate peaks, System suitability solution
Tailing factor: NMT 2.0, Standard solution
Relative standard deviation: NMT 2.0%, Standard solution
Analysis
Samples: Standard solution and Sample solution
Calculate the amount of lactate (C3H5O3) in each 100 mL of Injection taken:
Result = (r /r ) × C × (M /M ) × 100
r = peak response from the Sample solution
r = peak response from the Standard solution
C = concentration of USP Sodium Lactate RS in the Standard solution (mg/mL)
M = molecular weight of lactate, 89.07
M = molecular weight of anhydrous sodium lactate, 112.06
Acceptance criteria: 231.0–261.0 mg of lactate (C3H5O3) per 100 mL of Injection
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-May-2021)
pH 〈791〉: 6.0–7.5
Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉.
5 ADDITIONAL REQUIREMENTS
Packaging and Storage: Preserve 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. The label also includes the warning: “Not for use in the treatment of lactic acidosis”.
USP Reference Standards 〈11〉
USP Sodium Lactate RS
