Esmolol 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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Benzenepropanoic acid, 4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]-, methyl ester, hydrochloride, (±)-;

(±)-Methyl p-[2-hydroxy-3-(isopropylamino)propoxy]hydrocinnamate hydrochloride CAS RN^®: 81161-17-3; UNII: V05260LC8D.

1 DEFINITION

Esmolol Hydrochloride contains NLT 98.0% and NMT 102.0% of esmolol hydrochloride (C₁₆H₂₅NO₄· HCl),, calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197). Infrared Spectroscopy 197K

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

Buffer: Dissolve 3.0 g of potassium dihydrogen phosphate in 650 mL of water.

Mobile phase: Acetonitrile, methanol, and Buffer (150:200:650)

System suitability stock solution: 1 mg/ml. of USP Esmolol Hydrochloride RS prepared as follows. Transfer a suitable quantity of USP Esmolol Hydrochloride RS to an appropriate volumetric flask, and dissolve in and dilute with 1 N hydrochloric acid to volume. Allow the contents to stand for at least 30 min. [Norr-This results in the partial degradation of the esmolol resulting in the production of esmolol free acid (see System suitability for the relative retention times)]

System suitability solution: 0.2 mg/ml. of USP Esmolol Hydrochloride RS in water from the System suitability stock solution

Standard solution: 200 µg/mL of USP Esmolal Hydrochloride RS in water

Sample solution: 200 µg/mL of Esmolol Hydrochloride in water

Chromatographic system

(See Chromatography (621). System Suitability)

Mode: LC

Detector: UV 222 mm

Column: 3.9-mm x 30-cm; 10-um packing L1

Flow rate: 2 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for esmolol free acid and esmolol are 0.41 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 4.0 between esmolol free acid and esmolol, System suitability solution

Tailing factor: NMT 2.0 for the esmolol peak, System suitability solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of esmolol hydrochloride (C₁₆H₂₅NO₄· HCl) in the portion of the Esmolol Hydrochloride taken:

Result = (r_U/(r_S) × (C_S /C_U) x 100

r_U = peak response of esmolol from the Sample solution

r_S = peak response of esmolol from the Standard solution

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

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

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

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

ORGANIC IMPURITIES

Buffer and System suitability solution: Prepare as directed in the Assay.

Solution A: Methanol

Solution 8: Prepare as directed for Mobile phase in the Assay

Mobile phase: See Table 1.

Sample solution: 1 mg/mL of Esmolol Hydrochloride in water

Chromatographic system: Proceed as directed in the Assay, except include a column temperature of 30".

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 4.0 between esmolol free acid and esmolol

Tailing factor: NMT 2.0 for the esmolol peak

Analysis

Sample: Sample solution

Calculate the percentage of each individual impurity in the portion of Esmolol Hydrochloride taken:

Result = (r_u/r_t)x100

r_u = peak response of each individual impurity from the Sample solution

r_t = sum of all the peak responses from the Sample solution 

Acceptance criteria: See Table 2. Disregard any peak below 0.05%

^a 3-{4-[2-Hydroxy-3-(isopropylamino)propoxy]phenyl}propionic acid.

^b 3-{4-[2-Hydroxy-3-(isopropylamino)propoxy]phenyl}-N-isopropylpropionamide.

^c Methyl 3-{4-[3-(ethylamino)-2-hydroxypropoxy]phenyl}propionate.

^d Methyl 3-{4-[2-hydroxy-3-(3-{4-[2-hydroxy-3-(isopropylamino)propoxy]phenyl}-N-isopropylpropionamido)propoxy]phenyl}propionate.

5 SPECIFIC TESTS

pH (791)

Sample solution: 250 mg/mL of Esmolol Hydrochloride in water

Acceptance criteria: 3.0–5.0

Water Determination (921), Method I, Method Ia: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Protect from freezing, and store at room temperature.