Potassium 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

Potassium Citrate and Citric Acid Oral Solution is a solution of Potassium Citrate and Citric Acid in a suitable aqueous medium. In each 100 mL, it contains NLT 7.55 g and NMT 8.35 g of potassium (K), and NLT 12.18 g and NMT 13.46 g of citrate (C₆H₅O₇), equivalent to NLT 20.9 g and NMT 23.1 g of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O). It also contains NLT 6.34 g and NMT 7.02 g of citric acid monohydrate (C₆H₈O₇ · H₂O).

[Note - The potassium ion content of Oral Solution is approximately 2 mEq/mL.]

2 IDENTIFICATION

Change to read:

A. Potassium: The retention time of the potassium peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay, Procedure 1: Potassium. (USP 1-Aug-2022)

B.

Sample solution: Oral Solution and hydrochloric acid (50:50)

Analysis: To 2 mL of the Sample solution add 10 mL of cobalt–uranyl acetate TS, and stir with a glass rod.

Acceptance criteria: No precipitate or turbidity forms after 15 min, and the Sample solution remains clear (absence of sodium).

Change to read:

C. Citrate: The retention time of the citrate peak of the Sample solution corresponds to that of Standard solution 1, as obtained in the Assay, Procedure 2: Citrate. (USP 1-Aug-2022)

3 ASSAY

Change to read:

Procedure 1: (USP 1-Aug-2022) Potassium

Use water with a resistivity of NLT 18 megohm-cm to prepare the solutions.

Mobile phase: 4 mM nitric acid

System suitability solution: 40 μg/mL of USP Potassium Citrate RS and 15 μg/mL of magnesium¹ in water

Standard solution: 40 μg/mL of USP Potassium Citrate RS in water

Sample stock solution: Nominally 2 mg/mL of potassium citrate monohydrate prepared as follows. Transfer a suitable aliquot of Oral Solution to a suitable volumetric flask, and dilute with water to volume.

Sample solution: Nominally 40 μg/mL of potassium citrate monohydrate in water from the Sample stock solution

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Direct conductivity

Columns

Guard: 4-mm × 0.5-cm; 5-μm packing L76

Analytical: 4-mm × 15-cm; 5-μm packing L76

Column temperature: 30°

Flow rate: 0.9 mL/min

Injection volume: 20 μL

Run time: NLT 2 times the retention time of the potassium peak

System suitability

Samples: System suitability solution and Standard solution

[Note - The relative retention times for the potassium and magnesium ions are 1.0 and 1.3, respectively.]

Suitability requirements

Resolution: NLT 3.0 between the potassium and magnesium ions, 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 quantity, in g, of potassium (K) in each 100 mL of Oral Solution taken:

Result = (r_U/r_S) × (C_S/C_U) × L

r_U = peak response of potassium from the Sample solution

r_S = peak response of potassium from the Standard solution

C_S = concentration of USP Potassium Citrate RS in the Standard solution (μg/mL)

C_U = nominal concentration of potassium citrate monohydrate in the Sample solution (μg/mL)

L = label claim of potassium for Oral Solution (g/100 mL)▲ (USP 1-Aug-2022)

Acceptance criteria: 7.55–8.35 g of potassium (K) in each 100 mL

Change to read:

Procedure 2: (USP 1-Aug-2022) Citrate

Mobile phase, Standard solution (USP 1-Aug-2022) ¹, and Chromatographic system: Proceed as directed in the Assay for Citric Acid/Citrate and Phosphate 〈345〉.

Sample solution: Transfer 15 mL of Oral Solution to a suitable volumetric flask, and proceed as directed in the Sample solution (for the assay of citric acid/citrate) in 〈345〉.

Analysis

Samples: Standard solution (USP 1-Aug-2022) 1 and Sample solution (USP 1-Aug-2022)

Calculate the quantity, in g, of citrate (C₆H₅O₇) in each 100 mL of Oral Solution taken:

Result = {[(r_U/r_S) × (C_S/F) × D] − A × (M_r1/M_r2)} × V (USP 1-Aug-2022)

r_U = peak response of citrate from the Sample solution

r_S = peak response of citrate from Standard solution (USP 1-Aug-2022) 1

C_S = concentration of citrate in Standard solution (USP 1-Aug-2022) 1 (μg/mL)

F = conversion factor, 106μg/g

D = dilution factor for the Sample solution

A = concentration (USP 1-Aug-2022) of citric acid monohydrate in the Oral Solution determined in Assay, Procedure 3: Citric Acid (USP 1-Aug-2022) (g/mL)

M_r1 = molecular weight of citrate, 189.10

M_r2 = molecular weight of citric acid monohydrate, 210.14

V = volume of Oral Solution, 100 mL (USP 1-Aug-2022)

Acceptance criteria: 12.18–13.46 g of citrate (C₆H₅O₇), equivalent to 20.9–23.1 g of potassium citrate monohydrate (C₆H₅K₃O₇ · H₂O) and 6.34–7.02 g of citric acid monohydrate (C₆H₈O₇ · H₂O), in each 100 mL

Change to read:

Procedure 3: (USP 1-Aug-2022) Citric Acid

Sample solution: 15 mL of Oral Solution, dilute with water to 250 mL

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. Each milliliter of Titrant is equivalent to 1.401mg of citric acid monohydrate (C₆H₈O₇ · H₂O).

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

4 SPECIFIC TESTS

pH 〈791〉: 4.9–5.4

5 ADDITIONAL REQUIREMENTS

Change to read:

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.(USP 1-Aug-2022)

Add the following:

USP Reference Standards 〈11〉

USP Potassium Citrate RS (USP 1-Aug-2022)

¹ From commercially available National Institute of Standards and Technology (NIST)-traceable standard solution for magnesium.