Sodium Citrate and Citric Acid Oral Solution

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 Citrate and Citric Acid Oral Solution is a solution of Sodium Citrate and Citric Acid in a suitable aqueous medium. It contains, in each 100 mL, NLT 2.23 g and NMT 2.46 g of sodium (Na), and NLT 6.11 g and NMT 6.75 g of citrate (C₆H₅O₇), equivalent to NLT 9.5 g and NMT 10.5 g of sodium citrate dihydrate (C₆H₅Na₃O₇ · 2H₂O), and NLT 6.34 g and NMT 7.02 g of citric acid monohydrate (C₆H₈O₇ · H₂O).

2 IDENTIFICATION

A. Sodium Citrate and Citric Acid Oral Solution imparts an intense yellow color to a nonluminous flame.

B.

Sample solution: 2 mL of Oral Solution

Analysis: Add 2 mL of 15% potassium carbonate TS to the Sample solution, boil, and cool. Add 4 mL of potassium pyroantimonate TS.

Acceptance criteria: A dense precipitate is formed (indicates the presence of sodium).

C.

Sample solution: A dilution of Oral Solution (1 in 20)

Analysis: Add 5 mL of sodium cobaltinitrite TS to 2 mL of Sample solution.

Acceptance criteria: A yellow precipitate is not formed immediately (indicates the absence of potassium).

D. Identification Tests—General 〈191〉, Chemical Identification Tests, Citrate

Sample solution: 3–5 drops of Oral Solution

Analysis: Add 20 mL of a mixture of pyridine and acetic anhydride (3:1) to the Sample solution.

Acceptance criteria: A light red color is produced.

3 ASSAY

Sodium

Sodium stock solution: 58.44 mg/mL of sodium chloride prepared as follows. Transfer 14.61 g of sodium chloride, previously dried at 105° for 2 h, to a 250-mL volumetric flask. Dilute with water to volume.

Diluent: 1.04 mg/mL of lithium nitrate in water (equivalent to 15 mEq per 1000 mL of lithium) with a suitable nonionic surfactant

Standard stock solution: Pipet 50 mL of the Sodium stock solution into a 500-mL volumetric flask and dilute with water to volume.

Standard solution: Dilute 50 μL of the Standard stock solution with Diluent to 10 mL.

Sample stock solution: Transfer a volume of Oral Solution, equivalent to 1 g of sodium citrate dihydrate, to a 100-mL volumetric flask and dilute with water to volume.

Sample solution: Dilute 50 μL of the Sample stock solution with Diluent to 10 mL.

Blank: Diluent

Instrumental conditions

Mode: Flame photometry

Analytical wavelength: Sodium emission line at 589 nm

Analysis

Samples: Standard solution and Sample solution

Adjust the flame photometer to read zero with the Diluent. Concomitantly determine the sodium flame emission readings for the Standard solution and the Sample solution.

Calculate the quantity (g) of sodium (Na) in 100 mL of Oral Solution taken:

Result = (R_U,Na /R_S,Na) × (W/V) × F × (A_r /M_r ) × F₁

R_U,Na = sodium emission reading of the Sample solution

R_S,Na = sodium emission reading of the Standard solution

W = weight of sodium chloride in the Sodium stock solution (g)

V = volume of Oral Solution taken (mL)

F = ratio of the dilution factor of the Sample solution to the Standard solution, 0.04

A_r = atomic weight of sodium, 22.99

M_r = molecular weight of sodium chloride, 58.44

F₁ = conversion factor for each 100 mL of Oral Solution, 100 mL

Acceptance criteria: 2.23–2.46 g of sodium (Na) in each 100 mL of Oral Solution

Sodium Citrate

Cation-exchange column: Mix 10 g of styrene–divinylbenzene cation-exchange resin with 50 mL of water in a suitable beaker. Allow the resin to settle and decant the supernatant until a slurry of resin remains. Pour the slurry into a 15-mm × 30-cm glass chromatographic tube (having a sealed-in, coarse-porosity fritted disk and fitted with a stopcock), and allow to settle as a homogeneous bed. Wash the resin bed with about 100 mL of water, closing the stopcock when the water level is about 2 mm above the resin bed.

Sample solution: Transfer a volume of Oral Solution, equivalent to 1 g of sodium citrate dihydrate, to a 100-mL volumetric flask and dilute with water to volume.

Titrimetric system

Mode: Direct titration

Titrant: 0.02 N sodium hydroxide VS

Endpoint detection: Visual

Analysis

Sample: Sample solution

Pipet 5 mL of the Sample solution carefully onto the top of the resin bed in the Cation-exchange column. Place a 250-mL conical flask below the column, open the stopcock, and allow to flow until the solution has entered the resin bed. Elute the column with 60 mL of water at a flow rate of about 5 mL/min, collecting about 65 mL of the eluate. Add 5 drops of phenolphthalein TS to the eluate, swirl the flask, and titrate with Titrant. Record the buret reading and calculate the volume of Titrant consumed.

Calculate the quantity (g) of sodium citrate dihydrate (C₆H₅Na₃O₇ · 2H₂O) in 100 mL of the Oral Solution taken:

Result = {[V × N × F × (D/V_S)] − [(M_r1/M_r2) × C]} × F₁ × F₂

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

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

F = equivalency factor, 98.05 mg/mEq for sodium citrate dihydrate

D = dilution factor of the Sample solution, 20

V_S = volume of Oral Solution taken (mL)

M_r1 = molecular weight of sodium citrate dihydrate, 294.10

M_r2 = molecular weight of citric acid monohydrate, 210.14

C = concentration of citric acid monohydrate in the Sample solution, as obtained in the Assay for Citric Acid (mg/mL)

F₁ = conversion factor from mg to g, 0.001

F₂ = conversion factor for each 100 mL of Oral Solution, 100 mL

Acceptance criteria: 9.5–10.5 g of sodium citrate dihydrate (C₆H₅Na₃O₇ · 2H₂O) in each 100 mL of Oral Solution

Citric Acid

Sample solution: Transfer a volume of Oral Solution, equivalent to 0.67 g of citric acid monohydrate, to a 100-mL volumetric flask and dilute with water to volume.

Titrimetric system

Mode: Direct titration

Titrant: 0.02 N sodium hydroxide VS

Endpoint detection: Visual

Analysis

Sample: Sample solution

Transfer 5 mL of the Sample solution to a suitable flask. Add 25 mL of water and 5 drops of phenolphthalein TS. Titrate with Titrant to a pink endpoint. Record the buret reading and calculate the volume of Titrant consumed.

Calculate the quantity (g) of citric acid monohydrate (C₆H₈O₇ · H₂O) in 100 mL of Oral Solution taken:

Result = V × N × F × (D/V_S) × F₁ × F₂

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

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

F = equivalency factor, 70.05 mg/mEq for citric acid monohydrate

D = dilution factor of the Sample solution, 20

V_S = volume of Oral Solution taken (mL)

F₁ = conversion factor from mg to g, 0.001

F₂ = conversion factor for each 100 mL of Oral Solution, 100 mL

Acceptance criteria: 6.34–7.02 g of citric acid monohydrate (C₆H₈O₇ · H₂O) in each 100 mL of Oral Solution

4 PERFORMANCE TESTS

Deliverable Volume 〈698〉

For multiple-unit containers

Acceptance criteria: Meets the requirements

Uniformity of Dosage Units 〈905〉

For single-unit containers

Acceptance criteria: Meets the requirements

5 SPECIFIC TESTS

pH 〈791〉: 4.0–4.4

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.