Ephedrine Hydrochloride

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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Benzenemethanol, α-[1-(methylamino)ethyl]-, hydrochloride, [R-(R*,S*)]-;

(-)-Ephedrine hydrochloride;

(1R,2S)-2-(Methylamino)-1-phenylpropan-1-ol hydrochloride; CAS RN^®: 50-98-6; UNII: NLJ6390P1Z.

1 DEFINITION

Ephedrine Hydrochloride contains NLT 98.0% and NMT 102.0% of ephedrine hydrochloride (C₁₀H₁₅NO· HCl),, calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A.SPECTROSCOEIC IDENTIFICATION TERTS (197), Infrared Spectroscopy: 197K (CN 1-May-2020)

B. IDENTIFICATION TESTS GENERAL (191), Chemical Identification Tests, Chloride: Meets the requirements

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

3 ASSAY

PROCEDURE

Buffer: 11.6 g/L of ammonium acetate. Adjust with glacial acetic acid to a pH of 4.0.

Mobile phase: Methanol and Buffer (6:94)

Diluent: Methanol and water (6:94)

System suitability solution: 0.1 mg/ml each of LISP Ephedrine Hydrochloride RS and USP Pseudoephedrine Hydrochloride RS in Diluent

Standard solution: 0.2 mg/mL of USP Ephedrine Hydrochloride RS in Diluent

Sample solution: 0.2 mg/mL of Ephedrine Hydrochloride in Diluent

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: LC

Detector: UV 257 nm

Column: 4.6-mm x 15-cm; 3-um packing L11

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of ephedrine

System suitability

Samples: System suitability solution and Standard solution

[Note-The relative retention times for ephedrine and pseudoephedrine are 1.0 and 1.1, respectively.]

Suitability requirements

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

Tailing factor: NMT 2.0 for ephedrine, Standard solution

Relative standard deviation: NMT 0.73% for ephedrine, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ephedrine hydrochloride (C₁₀H₁₅NO· HCl) in the portion of Ephedrine Hydrochloride taken

Result = (r_U/(r_S) × (C_S /C_U) x 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 Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Ephedrine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

RESIDUE ON JONITION (281): NMT 0.1%

CHLORIDE AND SULFATE (221), Sulfate

Sample solution: 1.25 mg/mL of Ephedrine Hydrochloride in water

Analysis: Add 1 ml. of 3 N hydrochloric acid and 1 ml. of barium chloride TS to 40 ml of the Sample solution.

Acceptance criteria: No turbidity develops within 10 min.

ORGANIC IMPURITIES

Buffer, Mobile phase, and Chromatographic system: Proceed as directed in the Assay, except for the Run time.

Run time: NLT 2.5 times the retention time of ephedrine

System suitability solution: 0.1 mg/mL each of USP Ephedrine Hydrochloride RS and USP Pseudoephedrine Hydrochloride RS in Mobile

phase

Sensitivity solution: 3.8 µg/mL of USP Ephedrine Hydrochloride RS in Mobile phase

Standard solution: 30 µg/mL of USP Ephedrine Hydrochloride RS in Mobile phase

Sample solution: 7.5 mg/ml of Ephedrine Hydrochloride in Mobile phase

System suitability

Samples: System suitability solution, Sensitivity 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 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of e-acetylbenzyl alcohol or any unspecified impurity in the portion of Ephedrine Hydrochloride taken:

Result = (r_U/(r_S) × (C_S /C_U) × (1/F) ×100

r_U = peak response of a acetylbenzyl alcohol or any unspecified impurity from the Sample solution

r_S = peak response of ephedrine from the Standard solution

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

C_U = concentration of Ephedrine Hydrochloride in the Sample solution (mg/mL)

Frelative response factor (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%

^a Included for identication only. It is not to be reported and not to be included in the total impurities.

^b (-)-(1R)-1-Hydroxy-1-phenylpropan-2-one.

^c Excludes a-acetylbenzyl alcohol.

5 SPECIFIC TESTS

OPTICAL ROTATION (7815), Procedures. Specific Rotation

Sample solution: 50 mg/mL of Ephedrine Hydrochloride in water

Acceptance criteria: −33.0° to −35.5°

LOSS ON DEYING (731)

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 0.5%

ACIDITY OR ALKALINITY

Sample solution: 50 mg/ml. of Ephedrine Hydrochloride in water

Analysis: To 20 mL of Sample solution add 1 drop of methyl red TS.

Acceptance criteria: if the solution is yellow, it is changed to red by NMT 0.10 mL of 0.020 N sulfuric acid. If the solution is pink, it is changed to yellow by NMT 0.20 mL of 0.020 N sodium hydroxide.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed, light-resistant containers.