Multiple Electrolytes and Dextrose Injection Type 3

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

Multiple Electrolytes and Dextrose Injection Type 3 is a sterile solution of Dextrose and suitable salts in Water for Injection to provide sodium, potassium, and chloride ions. In addition, the salts provide ions of ammonium, or acetate and phosphate, or phosphate and lactate. It contains NLT 90.0% and NMT 110.0% of the labeled amounts of sodium (Na), potassium (K), ammonium (NH₄), acetate (C₂H₃O₂), phosphate (PO₄), and lactate (C₃H₅O₃); 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), Chloride and Ammonium: 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 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.

G. 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.

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 = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of acetate from the Sample solution

r_s = peak response of acetate from the Standard solution

C_s = concentration of acetate in the Standard solution (mEq/mL)

C_u = nominal concentration of acetate in the Sample solution (mEq/mL)

Acceptance criteria: 90.0%–110.0%

3.2 AMMONIUM (if present)

Sample solution: Transfer a volume of Injection, equivalent to 63 mg (3.5 mEq) of ammonium, to a 500-mL Kjeldahl flask. Dilute with water to 200 mL, and add 50 ml of sodium hydroxide solution (2 in 5).

Titrimetric system

Mode: Direct titration

Titrant: 0.1 N sulfuric acid VS

Endpoint detection: Visual

Analysis

Sample: Sample solution

Immediately connect the flask containing the Sample solution by means of a distillation trap to a well-cooled condenser, the delivery tube of which dips into 40 mL of boric acid solution (1 in 25) contained in a suitable receiver. Heat to boiling, and distill about 200 mL. Cool the liquid in the receiver, if necessary, then add methyl red TS, and titrate with Titrant. Perform a blank determination, and make any necessary correction.

Calculate the percentage of the labeled amount of ammonium (NH₄) in the portion of Injection taken:

Result = (V_S − V_B ) × N × (F/W) × 100

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

V_B = Titrant volume consumed by the blank (mL)

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

F = equivalency factor, 18.04 mg/mEq

W = nominal amount of ammonium in the Sample solution (mg)

Acceptance criteria: 90.0%-110.0%

3.3 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 about 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 × N × (F/W) × 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%

3.4 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 × a)/(l × α)] × (1/C_u ) × (M_r1 /M_r2 ) × 100

a = observed angular rotation of the Sample solution (°)

l = length of the polarimeter tube (dm)

α = midpoint of the specic rotation range for anhydrous dextrose, 52.9°

C_u = nominal concentration of dextrose in the Sample solution (g/100 mL)

M_r1 = molecular weight of dextrose monohydrate, 198.17

M_r2 = molecular weight of anhydrous dextrose, 180.16

Acceptance criteria: 90.0%–105.0%

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 = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of lactate from the Sample solution

r_s = peak response of lactate from the Standard solution

C_s = concentration of lactate in the Standard solution (mEq/mL)

C_u = nominal concentration of lactate in the Sample solution (mEq/mL)

Acceptance criteria: 90.0%–110.0%

3.6 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

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 mL each of the Standard solution, the Sample solution, and the Blank to separate test tubes.

To each test tube add 1 mL of Solution A, and allow to stand for 3 min. Add 1 mL of Solution B. Add 1 mL of Solution C, 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 = (A_u /A_s ) × (C_s /C_u ) × 100

A_u = absorbance of the Sample solution, corrected for any absorbance of the solution from the Blank

A_s = absorbance of the Standard solution, corrected for any absorbance of the solution from the Blank

C_s = concentration of phosphate in the Standard solution (mEq/mL)

C_u = nominal concentration of phosphate (PO₄ ) in the Sample solution (mEq/mL)

Acceptance criteria: 90.0%–110.0%

3.7 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, 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: 0.0391J mg/mL of potassium (K) from Potassium stock solution and 0.02299J mg/mL of sodium (Na) from Sodium stock solution prepared as follows. Transfer 0.1JmL of Potassium stock solution and 0.1 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 = (R_u /R_s ) × (C_s /C_u ) × 100

R_u = emission reading ratio of potassium to lithium from the Sample solution

R_s = emission reading ratio of potassium to lithium from the Standard solution

C_s = concentration of potassium (K) in the Standardsolution (mg/mL)

C_u = 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 = (R_u /R_s ) × (C_s /C_u ) × 100

R_u = emission reading ratio of sodium to lithium from the Sample solution

R_s = emission reading ratio of sodium to lithium from the Standard solution

C_s = concentration of sodium (Na) in the Standard solution (mg/mL)

C_u = 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%

4 SPECIFIC TESTS

BACTERIAL ENDOTOXINS TEST (85): NMT 0.5 USP Endotoxin Units/mL

PH (791); 4.0-6.5

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 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 Sodium Lactate RS