Ephedrine Sulfate Injection

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

Ephedrine Sulfate Injection is a sterile solution of Ephedrine Sulfate in Water for Injection. It contains NLT 95.0% and NMT 105.0% of the labeled amount of ephedrine sulfate [(C₁₀H₁₅NO)₂ · H₂SO₄].

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

Sample: Mix 1 mL of Injection with 5 mL of alcohol, and evaporate on a steam bath with the aid of a current of air to dryness.

Acceptance criteria: The residue obtained from the Sample meets the requirements.

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Solution A: To 1 L of water add 4 mL of triethylamine. Adjust with phosphoric acid to a pH of 4.0.

Mobile phase: Acetonitrile and Solution A (1:99)

System suitability solution: 0.1 mg/mL of USP Ephedrine Sulfate RS and 0.01 mg/mL of USP Pseudoephedrine Sulfate RS in water

Standard solution: 0.1 mg/mL of USP Ephedrine Sulfate RS in water

Sample solution: Nominally 0.1 mg/mL of ephedrine sulfate in water prepared as follows. Transfer a portion of Injection to a suitable volumetric flask. Dilute with water to volume, and mix well.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 206 nm

Column: 2.1-mm × 10-cm; 2.6-μm packing L11

Column temperature: 30°

Flow rate: 0.6 mL/min

Injection volume: 10 μL

Run time: NLT 3 times the retention time of ephedrine

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between ephedrine and pseudoephedrine, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ephedrine sulfate [(C₁₀H₁₅NO)₂ · H₂SO₄] in the portion of Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U= peak response of ephedrine from the Sample solution

r_S = peak response of ephedrine from the Standard solution

C_S = concentration of USP Ephedrine Sulfate RS in the Standard solution (mg/mL)

C_U = nominal concentration of ephedrine sulfate in the Sample solution (mg/mL)

Acceptance criteria: 95.0%–105.0%

4 IMPURITIES

Organic Impurities

Mobile phase, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 1.0 μg/mL of USP Ephedrine Sulfate RS in water

Sample solution: Nominally 500 μg/mL of ephedrine sulfate in water prepared as follows. Transfer a portion of Injection to a suitable volumetric flask. Dilute with water to volume, and mix well.

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between ephedrine and pseudoephedrine, System suitability solution

Relative standard deviation: NMT 2.0% for ephedrine, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of ephedrine from the Standard solution

C_S = concentration of USP Ephedrine Sulfate RS in the Standard solution (μg/mL)

C_U = nominal concentration of ephedrine in the Sample solution (μg/mL)

Acceptance criteria: See Table 1. Disregard any peak less than 0.05%.

Table 1

^a Process impurity included in the table for identification only. Process impurities are controlled in the drug substance, and are not to be reported or included in the total impurities of the drug product.

5 SPECIFIC TESTS

pH 〈791〉: 4.5–7.0

Other Requirements: Meets the requirements in Injections and Implanted Drug Products 〈1〉

Bacterial Endotoxins Test 〈85〉: NMT 1.7 USP Endotoxin Units/mg of ephedrine sulfate

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or multiple-dose, light-resistant containers, preferably of Type I glass. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Ephedrine Sulfate RS

USP Pseudoephedrine Sulfate RS (C₁₀H₁₅NO)₂ · H₂SO₄ 428.54