Multiple Electrolytes and Dextrose Injection Type 1
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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
Multiple Electrolytes and Dextrose Injection Type 1 is a sterile solution of Dextrose and suitable salts in Water for Injection to provide sodium, potassium, magnesium, and chloride ions. In addition, the salts provide ions of acetate, or acetate and gluconate, or acetate and phosphate, or phosphate and lactate, or phosphate and sulfate. It contains NLT 90.0% and NMT 110.0% of the labeled amounts of sodium (Na), potassium (K), magnesium (Mg), acetate (C2H3O2), gluconate (C6H11O7), phosphate (PO4), lactate (C3H5O3), and sulfate (SO); NLT 90.0% and NMT 120.0% of the labeled amount of chloride (CI); and NLT 90.0% and NMT 105.0% of the labeled amount of dextrose (C6H12O6 · H2O). It may contain Hydrochloric Acid or Sodium Hydroxide used to adjust the pH. It contains no antimicrobial agents.
2 IDENTIFICATION
A.
Sample solution: Nominally 50 mg/mL of dextrose from a suitable volume of Injection
Analysis: Add a few drops of the Sample solution to 5 mL of hot alkaline cupric tartrate TS.
Acceptance criteria: A copious red precipitate of cuprous oxide is formed.
B. IDENTIFICATION TESTS GENERAL (191), Magnesium and Chloride: Meets the requirements
C. SODIUM: The sample imparts an intense yellow color to a nonluminous flame.
D. 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.]
E. Where acetate is purported to be present, the retention time of the acetate peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay for Acetate.
F. Where gluconate is purported to be present, the retention time of the gluconate peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay for Gluconate.
G. Where phosphate is purported to be present, proceed as follows.
Sample solution: Add 5 mL of Injection and 1 mL of ammonium molybdate TS to a test tube and mix.
Acceptance criteria: A yellow precipitate, which is soluble in 6 N ammonium hydroxide, is formed.
H. Where lactate is purported to be present, 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,
I. IDENTIFICATION TESTS GENERAL (191), Sulfate: Where sulfate is purported to be present, it meets the requirements of test A.
3 ASSAY
3.1 ACETATE (if present)
Mobile phase: 0.05 N sulfuric acid
Standard solution: 1.2 mg/mL of sodium acetate trihydrate (0.0088 mEq/mL of acetate) in water
Sample solution: Nominally 0.0088 mEq/mL of acetate from a volume of Injection in water
Chromatographic system
(See Chromatography (621), System Suitability.)
Mode: LC
Detector: UV 210 nm
Columns
Guard: 4.6-mm x 3-cm; packing L17
Analytical: 7.8-mm x 30-cm; packing L17
Column temperature: 60°
Flow rate: 0.8 mL/min
Injection volume: 20 µL
System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of acetate (C2H3O2) in the portion of Injection taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response of acetate from the Sample solution
rS = peak response of acetate from the Standard solution
CS = concentration of acetate in the Standard solution (mEq/mL)
CU = nominal concentration of acetate in the Sample solution (mEq/mL)
Acceptance criteria: 90.0%-110.0%
3.2 CHLORIDE
Sample solution: Transfer a volume of Injection, equivalent to 55 mg of chloride (1.55 mEq), to a suitable conical flask, and add water, if necessary, to bring the volume to 10 mL. Add 10 mL of glacial acetic acid, 75 mL of methanol, and 0.5 mL 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 percentage of the labeled amount of chloride (CI) in the portion of Injection taken:
Result = V x N x (F/W) x 100
V = Titrant volume consumed by the Sample solution (mL)
N = actual normality of the Titrant (mEq/mL)
F = equivalency factor, 35.45 mg/mEq
W = nominal amount of chloride in the Sample solution (mg)
Acceptance criteria: 90.0%–120.0%
3.3 DEXTROSE
Sample solution: Transfer a volume of Injection containing 2–5 g of dextrose to a 100-mL volumetric flask. Add 0.2 mL of 6 N ammonium hydroxide, and dilute with water to volume.
Analysis
Sample: Sample solution
Determine the angular rotation in a polarimeter tube (see Optical Rotation 〈781〉).
Calculate the percentage of the labeled amount of dextrose (C6H12O6 · H2O) in the portion of Injection taken:
Result = [(100 x a)/(I x α)] x (1/CU) x (Mr1/Mr2) x 100
a = observed angular rotation of the Sample solution (")
I = length of the polarimeter tube (dm)
α = midpoint of the specific rotation range for anhydrous dextrose, 52.9"
CU = nominal concentration of dextrose in the Sample solution (g/100 mL)
Mr1 = molecular weight of dextrose monohydrate, 198.17
Mr2 = molecular weight of anhydrous dextrose, 180.16
Acceptance criteria: 90.0%-105.0%
3.4 GLUCONATE (if present)
Mobile phase: Dissolve 7.0 g of calcium acetate in 1900 mL of water, and adjust with glacial acetic acid to a pH of 4.5 ± 0.1. Dilute with water to 2000 mL, mix, pass through a filter of 0.5-µm pore size or finer, and degas. Maintain the Mobile phase at 70 +2° at all times.
System suitability solution: 5 mg/ml each of USP Sodium Lactate RS and USP Potassium Gluconate RS in water
Standard solution: 4.6 mg/mL of USP Potassium Gluconate RS (0.02 mEq/mL of gluconate) in water
Sample solution: Nominally 0.023 mEq/mL of gluconate from a volume of Injection in water
Chromatographic system
(See Chromatography (621), System Suitability.)
Mode: LC
Detector: Refractive index
Column: 7.8-mm x 30-cm; packing L19 in the calcium form. Condition the column with Mobile phase for 60 min.
Column temperature: 70 ± 2°
Flow rate: 1 mL/min
Injection volume: 50 µL
System suitability
Samples: System suitability solution and Standard solution
Suitability requirements
Resolution: NLT 4.0 between lactate and gluconate, System suitability solution
Relative standard deviation: NMT 2.0%, Standard solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of gluconate (C6H11O7) in the portion of Injection taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response of gluconate from the Sample solution
rS = peak response of gluconate from the Standard solution
CS = concentration of gluconate in the Standard solution (mEq/mL)
CU = nominal concentration of gluconate in the Sample solution (mEq/mL)
Acceptance criteria: 90.0%-110.0%
3.5 LACTATE (if present)
Mobile phase: Formic acid, dicyclohexylamine, 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: 2 mg/mL of USP Sodium Lactate RS (0.018 mEq/mL of lactate) in water
Sample solution
For Injections containing >20 mEq/L of lactate: Nominally 0.02 mEq/mL of lactate from Injection in water
For Injections containing ≤20 mEq/L of lactate: Use the undiluted Injection.
Chromatographic system
(See Chromatography (621), System Suitability.)
Mode: LC
Detector: UV 210 nm
Column: 4.6-mm x 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 acetate and lactate, 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 percentage of the labeled amount of lactate (C3H5O3) in the portion of Injection taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response of lactate from the Sample solution
rS = peak response of lactate from the Standard solution
CS = concentration of lactate in the Standard solution (mEq/mL)
CU = nominal concentration of lactate in the Sample solution (mEq/mL)
Acceptance criteria: 90.0%-110.0%
3.6 MAGNESIUM
[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: 88.45 g/L of lanthanum chloride prepared as follows. Transfer a suitable quantity of lanthanum chloride to an appropriate volumetric flask. Add 50% of the final flask volume of water. Carefully add 25% of the final flask volume of hydrochloric acid. Mix, and allow to cool. Dilute with water to volume.
Solution B: Mix 678 mL of hydrochloric acid with water to make 3000 mL.
Standard stock solution A: 1.00 mg/ml. of magnesium (Mg) prepared as follows. Transfer 1.00 g of magnesium metal to a 1000-mL volumetric flask containing 10 mL of water. Slowly add 10 mL of hydrochloric acid, and swirl to dissolve the metal. Dilute with Solution B to volume.
Standard stock solution B: 100 µg/ml. of magnesium (Mg) prepared as follows. Transfer 10.0 mL of Standard stock solution A to a 100-mL volumetric flask, and dilute with Solution B to volume.
Standard solutions: 10.0, 15.0, and 20.0 µg/mL of magnesium (Mg) prepared as follows. To three separate 100-mL volumetric flasks, each containing 5.0 mL of Solution A, add 10.0, 15.0, and 20.0 mL, respectively, of Standard stock solution B. Dilute the contents of each flask with Solution B to volume.
Sample solution: Transfer a volume of Injection, equivalent to 20 mg of magnesium (Mg) to a 1000-mL volumetric flask containing 50.0 mL of Solution A. Dilute with Solution B to volume.
Blank: 5.0 mL of Solution A diluted with Solution B to 100.0 mL
Instrumental conditions
(See Atomic Absorption Spectroscopy (852).)
Mode: Atomic absorption spectrophotometry
Analytical wavelength: Magnesium emission line at 285.2 nm
Lamp: Magnesium hollow-cathode
Flame: Air-acetylene
Analysis
Samples: Standard solutions, Sample solution, and Blank
Plot the absorbances of the Standard solutions versus the concentration, in µg/mL, of magnesium (Mg), and draw the straight line best fitting the three plotted points. From the graph so obtained, determine the concentration (C) in µg/mL, of magnesium (Mg) in the Sample solution.
Calculate the percentage of the labeled amount of magnesium (Mg) in the portion of Injection taken:
Result = (C/CU) x 100
C = concentration of magnesium (Mg) in the Sample solution (µg/mL), interpolated from the graph obtained
CU = nominal concentration of magnesium (Mg) in the Sample solution (µg/mL)
Acceptance criteria: 90.0%-110.0%
3.7 PHOSPHATE (if present)
Solution A: 50 g/L of ammonium molybdate prepared as follows. Transfer a suitable amount of ammonium molybdate to an appropriate volumetric flask. Add 60% of the final flask volume of water, and swirl to dissolve. Add 15% of the flask volume of sulfuric acid, and swirl. Allow to cool, and dilute with water to volume.
Solution B: Dissolve 0.5 g of Hydroquinone in 100 mL of water, and add 1 drop of sulfuric acid. Prepare this solution fresh daily.
Solution C: Dissolve 1 g of sodium sulfite in water to make 5 mL. Prepare this solution fresh daily.
Standard solution: 0.11 mg/ml of monobasic potassium phosphate (0.0008 mEq/mL of phosphate) in water
Sample solution: Nominally 0.0008 mEq/mL of phosphate from a volume of Injection in water
Blank: Water
Instrumental conditions
Mode: Vis
Analytical wavelength: 640 nm
Analysis
Samples: Standard solution, Sample solution, and Blank
Use water to zero the instrument. Transfer 2.0 mL each of the Standard solution, Sample solution, and the Blank to separate test tubes. To each test tube add 1.0 mL of Solution A, mix, and allow to stand for 3 min. Add 1.0 mL of Solution B, and mix. Add 1.0 mL of Solution C, mix, and allow to stand for 30 min.
Calculate the percentage of the labeled amount of phosphate (PO4) in the portion of the Injection taken:
Result = (AU/AS) × (CS/CU) × 100
AU = absorbance of the Sample solution, corrected for any absorbance of the solution from the Blank
AS = absorbance of the Standard solution, corrected for any absorbance of the solution from the Blank
CS = concentration of phosphate (PO) in the Standard solution (mEq/mL)
CU = nominal concentration of phosphate (PO) in the Sample solution (mEq/mL)
Acceptance criteria: 90.0%-110.0%
3.8 POTASSIUM AND SODIUM
Internal standard solution: 1.04 mg/mL of lithium nitrate prepared as follows. Transfer 1.04 g of lithium nitrate to a 1000-ml volumetric flask. Add a suitable nonionic surfactant, and then dilute with water to volume.
Potassium stock solution: 74.56 mg/mL of potassium chloride (1 mEq/mL of potassium) prepared as follows. Transfer 18.64 g of potassium chloride, previously dried at 105° for 2 h, to a 250-mL volumetric flask, and dilute with water to volume.
Sodium stock solution: 58.44 mg/mL of sodium chloride (1 mEq/mL of sodium) prepared as follows. Transfer 14.61 g of sodium chloride, previously dried at 105° for 2 h, to a 250-mL volumetric flask, and dilute with water to volume.
Standard stock solution: 0.0391Jmg/mL of potassium (K) from Potassium stock solution and 0.02299J mg/mL of sodium (Na) from Sodium stock solution prepared as follows. Transfer 0.1J mL of Potassium stock solution and 0.1J mL of Sodium stock solution to a 100-mL volumetric flask, where J and J' are the labeled amounts, in mEq/L, of potassium and sodium, respectively, in the Injection. Dilute with water to volume.
Standard solution: Dilute 5.0 mL of Standard stock solution with Internal standard solution to 500.0 mL.
Sample solution: Dilute 5.0 mL of Injection with Internal standard solution to 500.0 mL.
Instrumental conditions
Mode: Flame photometer
Analytical wavelengths
Potassium: Maximum at 766 nm
Sodium: Maximum at 589 nm
Lithium: Maximum at 671 nm
Blank: Internal standard solution
Analysis
Samples: Standard solution, Sample solution, and Blank
Use the Blank to zero the instrument. Concomitantly determine the flame emission readings for the Standard solution and Sample solution.
Calculate the percentage of the labeled amount of potassium (K) in the portion of Injection taken:
Result = (RU/RS) × (CS/CU) × 100
RU = emission reading ratio of potassium to lithium from the Sample solution
RS = emission reading ratio of potassium to lithium from the Standard solution
CS = concentration of potassium (K) in the Standardsolution (mg/mL)
CU = nominal concentration of potassium (K) in the Sample solution (mg/mL)
[NOTE-Each mg of potassium (K) is equivalent to 0.02558 mEq of potassium (K).]
Calculate the percentage of the labeled amount of sodium (Na) in the portion of Injection taken:
Result = (RU/RS) × (CS/CU) × 100
RU = emission reading ratio of sodium to lithium from the Sample solution
RS = emission reading ratio of sodium to lithium from the Standard solution S
CS = concentration of sodium (Na) in the Standard solution (mg/mL)
CU = nominal concentration of sodium (Na) in the Sample solution (mg/mL)
[NOTE-Each mg of sodium (Na) is equivalent to 0.04350 mEq of sodium (Na).]
Acceptance criteria
Potassium: 90.0%~110.0%
Sodium: 90.0%-110.0%
3.9 SULFATE (if present)
Sample solution: Equivalent to 120 mg (1.25 mEq) of sulfate from a volume of injection. Dilute, if necessary, to 200 mL, and add 1 mL of hydrochloric acid.
Analysis: Heat the Sample solution to boiling, and gradually add in small portions and while constantly stirring, an excess of hot barium chloride TS (about 8 mL). Heat the mixture on a steam bath for 1 h, collect the precipitate of barium sulfate on a tared filtering crucible, wash until free from chloride, dry, ignite, and weigh.
Calculate the percentage of the labeled amount of sulfate (SO4) in the portion of Injection taken:
Result = {[W x (Mr1/Mr2) x (1/Mr1)]/(L x V)} x 100
W = weight of barium sulfate after ignition (mg)
Mr1 = molecular weight of sulfate, 96.06
Mr2 = 1 molecular weight of barium sulfate, 233.43
L = label claim of sulfate in the Injection (mEq/mL)
V = volume of Injection in the Sample solution (mL)
Acceptance criteria: 90.0%-110.0%
4 SPECIFIC TESTS
BACTERIAL ENDOTOXINS TEST (85): NMT 0.5 USP Endotoxin Units/mL
PH (791): 4.0-6.5
OTHER REQUIREMENTS: 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 content of each electrolyte in terms of milliequivalents (mEq) in a given volume. The label states the total osmolar concentration in mosmol/L. When the contents are less than 100 mL, the label alternatively may state the total osmolar concentration in mOsmol/mL
USP REFERENCE STANDARDS (11)
USP Potassium Gluconate RS
USP Sodium Lactate RS
