Oral Rehydration Salts

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

Oral Rehydration Salts is a dry mixture of Sodium Chloride, Potassium Chloride, Sodium Bicarbonate, and Dextrose (anhydrous). Alternatively, it may contain Sodium Citrate (anhydrous or dihydrate) instead of Sodium Bicarbonate. It may contain Dextrose (monohydrate) instead of Dextrose (anhydrous), provided that the Sodium Bicarbonate or Sodium Citrate is packaged in a separate, accompanying container. It contains the equivalent of NLT 90.0% and NMT 110.0% of the amounts of sodium (Na), potassium (K), chloride (Cl), and bicarbonate (HCO₃⁻) or citrate (C₆H₅O₇³⁻) calculated from the labeled amounts of Sodium Chloride, Potassium Chloride, and Sodium Bicarbonate [or Sodium Citrate (anhydrous or dihydrate)]. It contains NLT 90.0% and NMT 110.0% of the labeled amounts of anhydrous dextrose (C₆H₁₂O₆) or dextrose monohydrate (C₆H₁₂O₆ · H₂O). It may contain suitable ￾avors.

2 IDENTIFICATION

A. Sodium: The sample imparts an intense yellow color to a nonluminous ￾ame.

B. Potassium: The sample imparts a violet color to a nonluminous ￾ame. Since the presence of small quantities of sodium masks the color, screen out the yellow color produced by sodium by viewing through a blue ￾lter 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 ￾lters are commercially available.]

C. Identification Tests—General 〈191〉, Chloride: Meets the requirements

D. Identification Tests—General 〈191〉, Bicarbonate

Analysis: Collect the gas that evolves upon dissolution.

Acceptance criteria: Where it contains Sodium Bicarbonate, it dissolves with effervescence, and the collected gas so obtained meets the requirements in test A.

E. Identification Tests—General 〈191〉, Citrate

Sample solution: Constitute the Oral Rehydration Salts as directed in the labeling.

Analysis: Add 3–5 drops of the Sample solution to 20 mL of the mixture of pyridine and acetic anhydride.

Acceptance criteria: Where it contains Sodium Citrate, it meets the requirements.

F.

Sample solution: Constitute the Oral Rehydration Salts as directed in the labeling.

Analysis: Add a few drops of the Sample solution to 5 mL of hot alkaline cupric tartrate TS.

Acceptance criteria: Where it contains Dextrose, a copious red precipitate of cuprous oxide is formed (presence of dextrose).

3 ASSAY

Dextrose

Sample stock solution: Nominally 200 mg/mL of dextrose from Oral Rehydration Salts prepared as follows. Transfer the contents of 1 or more unit-dose containers of Oral Rehydration Salts, or a portion of the contents of 1 multiple-unit container equivalent to 20 g of dextrose, to a 100-mL volumetric ￾ask. Dilute with water to volume.

Sample solution: Nominally 100 mg/mL of dextrose from the Sample stock solution prepared as follows. Transfer 50.0 mL of the Sample stock solution to a 100-mL volumetric ￾ask. Add 0.2 mL of 6 N ammonium hydroxide, and dilute with water to volume.

[Note—Reserve the remaining Sample stock solution for the Assay procedures for Sodium and Potassium, Chloride, Bicarbonate, and Citrate.]

Analysis: Determine the angular rotation in a suitable polarimeter tube (see Optical Rotation 〈781A〉, Angular Rotation).

Sample: Sample solution

Where Oral Rehydration Salts is labeled to contain anhydrous dextrose, calculate the observed concentration (g/100 mL) of anhydrous dextrose (C₆H₁₂O₆) in the portion of Oral Rehydration Salts taken:

Result = (100 × a)/(l × α)

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

l = length of the polarimeter tube (dm)

α = midpoint of the speci￾c rotation range for anhydrous dextrose, 52.9°

Where Oral Rehydration Salts is labeled to contain dextrose monohydrate, calculate the observed concentration (g/100 mL) of dextrose monohydrate (C₆H₁₂O₆ · H₂O) in the portion of Oral Rehydration Salts taken:

Result = [(100 × a)/(l × α)] × (M/Mₐ)

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

l = length of the polarimeter tube (dm)

α = midpoint of the speci￾c rotation range for anhydrous dextrose, 52.9°

M = molecular weight of dextrose monohydrate, 198.17

Mₐ = molecular weight of anhydrous dextrose, 180.16

Calculate the percentage of the labeled amount of anhydrous dextrose (C₆H₁₂O₆) or dextrose monohydrate (C₆H₁₂O₆ · H₂O) in the portion of Oral Rehydration Salts taken:

Result = (Cᵤ/Cₛ) × 100

Cᵤ = observed concentration of the Sample solution (g/100 mL)

Cₛ = nominal concentration of the Sample solution (g/100 mL)

Acceptance criteria: 90.0%–110.0%

Sodium and Potassium

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 ￾ask, and dilute with water to volume.

Potassium stock solution: 74.56 mg/mL of potassium chloride prepared as follows. Transfer 18.64 g of potassium chloride, previously dried at 105° for 2 h, to a 250-mL volumetric ￾ask, and dilute with water to volume.

Diluent: 1.04 mg/mL of lithium nitrate prepared as follows. Transfer 1.04 g of lithium nitrate to a 1000-mL volumetric ￾ask. Add a suitable nonionic surfactant, then add water to volume.

Standard stock solution: 0.5844 mg/mL of sodium chloride and 0.7456 mg/mL of potassium chloride in water from the Sodium stock solution and the Potassium stock solution, respectively.

Standard solution: 0.01150 mg/mL of sodium and 0.01955 mg/mL of potassium from the Standard stock solution in Diluent.

Sample stock solution A: Nominally 0.23 mg/mL of sodium from the Sample stock solution remaining from the Assay for Dextrose in water.

Sample solution A: Nominally 0.0115 mg/mL of sodium from Sample stock solution A in Diluent.

Sample stock solution B: Nominally 0.39 mg/mL of potassium from the Sample stock solution remaining from the Assay for Dextrose in water.

Sample solution B: Nominally 0.01955 mg/mL of potassium from Sample stock solution B in Diluent.

Instrumental conditions

Mode: Flame photometer

Analytical wavelengths

Potassium: 766 nm

Sodium: 589 nm

Blank: Diluent

Analysis

Samples: Standard solution, Sample solution A, Sample solution B, and Blank

Use the Blank to zero the instrument. Measure the emission responses for the Standard solution, Sample solution A, and Sample solution B.

Calculate the percentage of the labeled amount of sodium (Na):

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

Calculate the percentage of the labeled amount of potassium (K):

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

Acceptance criteria

Sodium: 90.0%–110.0%

Potassium: 90.0%–110.0%

Chloride

Sample solution: Transfer a volume of the Sample stock solution remaining from the Assay for Dextrose, containing nominally 55 mg of chloride (Cl), to a suitable container.

Titrimetric system

Mode: Direct titration

Titrant: 0.1 N silver nitrate VS

Endpoint detection: Visual

Analysis

Sample: Sample solution

Titrate with Titrant until the silver chloride ￾occulates and the mixture acquires a faint pink color, using potassium chromate TS as the indicator.

Result = V × N × (F/W) × 100

V = volume of Titrant consumed (mL)

N = normality of Titrant (mEq/mL)

F = equivalent weight of chloride, 35.45 mg/mEq

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

Acceptance criteria: 90.0%–110.0%

Bicarbonate (if present)

Sample solution: Transfer a volume of the Sample stock solution remaining from the Assay for Dextrose, containing nominally 100 mg of bicarbonate, to a suitable beaker.

Titrimetric system

Mode: Direct titration

Titrant: 0.1 N hydrochloric acid VS

Endpoint detection: Visual

Analysis

Sample: Sample solution

Add 25 mL of water and 3 drops of methyl orange TS to the Sample solution. Titrate the resulting solution with Titrant.

Result = V × N × (F/W) × 100

N = normality of Titrant (mEq/mL)

F = equivalent weight of bicarbonate, 61.02 mg/mEq

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

Acceptance criteria: 90.0%–110.0%

Citrate (if present)

Mobile phase, Standard solution 1, and Chromatographic system: Proceed as directed in Assay for Citric Acid/Citrate and Phosphate 〈345〉.

Sample solution: Transfer a volume of the Sample stock solution remaining from the Assay for Dextrose, containing nominally 180 mg of citrate, to a suitable volumetric ￾ask, and proceed as directed.

Analysis

Samples: Standard solution 1 and Sample solution

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Minimum Fill 〈755〉: Meets the requirements.

[Note—In performing the Assay procedures for Sodium and Potassium, Chloride, and Bicarbonate or Citrate, calculate from the labeled amounts of sodium chloride, potassium chloride, and sodium bicarbonate or sodium citrate the total equivalent amounts of sodium (Na), potassium (K), chloride (Cl), and bicarbonate (HCO₃⁻) or citrate (C₆H₅O₇³⁻) contained therein (see Table 1).]

Table 1. mg Equivalent of Each g of Component

5 SPECIFIC TESTS

pH 〈791〉

Sample solution: Constitute the Oral Rehydration Salts as directed in the labeling.

Acceptance criteria: 7.0–8.8

Loss on Drying 〈731〉

Analysis: Dry at 50° to constant weight.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and avoid exposure to temperatures in excess of 30°. The Sodium Bicarbonate or Sodium Citrate component may be omitted from the mixture and packaged in a separate, accompanying container.

Labeling: The label indicates prominently whether Sodium Bicarbonate or Sodium Citrate is a component by the placement of the word “Bicarbonate” or “Citrate”, as appropriate, in juxtaposition to the o￾cial title. The label states the name and quantity, in g, of each component in each unit-dose container, or in a stated quantity, in g, of Oral Rehydration Salts in a multiple-unit container. The label states the net weight in each container and provides directions for constitution. Where packaged in individual unit-dose pouches, the label instructs the user not to open the pouch until the time of use. The label also states that any solution that remains unused 24 h after constitution is to be discarded.