Betaxolol 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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C₁₈H₂₉NO₃ · HCl 343.89

2-Propanol, 1-[4-[2-(cyclopropylmethoxy)ethyl]phenoxy]-3-[(1-methylethyl)amino]-, hydrochloride, (±)-;

(±)-1-[p-[2-(Cyclopropylmethoxy)ethyl]phenoxy]-3-(isopropylamino)-2-propanol hydrochloride

CAS RN®: 63659-19-8; UNII: 6X97D2XT0O.

1 DEFINITION

Betaxolol Hydrochloride contains NLT 98.0% and NMT 102.0% of betaxolol hydrochloride (C₁₈H₂₉NO₃ · HCl), calculated on the dried basis.

2 IDENTIFICATION

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.

C. Identification Tests—General 〈191〉, Chemical Identification Tests, Chloride

Analysis: Proceed as directed for amine hydrochlorides. (USP 1-May-2021)

Acceptance criteria: Meets the requirements

3 ASSAY

Procedure

Buffer: 3.4 g/L of monobasic potassium phosphate in water, adjusted with phosphoric acid to a pH of 3.0

Mobile phase: Acetonitrile, methanol, and Buffer (175:175:650)

Standard solution: 1 mg/mL of USP Betaxolol Hydrochloride RS in Mobile phase. Sonicate if necessary.

Sample solution: 1 mg/mL of Betaxolol Hydrochloride in Mobile phase. Sonicate if necessary.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 222 nm

Column: 4.6-mm × 25-cm; 5-µm packing L7

Flow rate: 1.5 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 3.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of betaxolol hydrochloride (C₁₈H₂₉NO₃ · HCl) in the portion of Betaxolol Hydrochloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Cₛ = concentration of USP Betaxolol Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = concentration of Betaxolol Hydrochloride in the Sample solution (mg/mL)

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Buffer, Mobile phase, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 1 mg/mL of USP Betaxolol Hydrochloride RS and 30 µg/mL of USP Betaxolol Related Compound A RS in Mobile phase

Standard solution: 0.003 mg/mL of USP Betaxolol Hydrochloride RS in Mobile phase

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for betaxolol related compound A and betaxolol are 0.9 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between the betaxolol related compound A and betaxolol peaks, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Identify the impurities in the Sample solution on the basis of the relative retention times in Table 1.

Calculate the percentage of each impurity in the portion of Betaxolol Hydrochloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × (1/F) × 100

rᵤ = peak response of each impurity from the Sample solution

rₛ = peak response of betaxolol from the Standard solution

Cₛ = concentration of USP Betaxolol Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = concentration of Betaxolol Hydrochloride in the Sample solution (mg/mL)

F = relative response factor for each individual impurity (see Table 1)

Acceptance criteria: See Table 1.

a. 1-[4-(2-Hydroxyethyl)phenoxy]-3-(isopropylamino)propan-2-ol.

b. 1-(4-Ethylphenoxy)-3-(isopropylamino)propan-2-ol.

c. 4-[2-(Cyclopropylmethoxy)ethyl]phenol.

d. 1-[4-(2-Butoxyethyl)phenoxy]-3-(isopropylamino)propan-2-ol.

e. 2-({[4-(2-Cyclopropylmethoxy)ethyl]phenoxy}methyl)oxirane.

5 SPECIFIC TESTS

pH 〈791〉

Sample solution: 20 mg/mL

Acceptance criteria: 4.5–6.5

Loss on Drying 〈731〉

Analysis: Dry under vacuum at 65° for 2 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at room temperature.

USP Reference Standards 〈11〉

USP Betaxolol Hydrochloride RS

USP Betaxolol Related Compound A RS

1-(4-Ethylphenoxy)-3-(isopropylamino)propan-2-ol.

C₁₄H₂₁NO₂ 237.34