Atenolol

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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Atenolol

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C₁₄H₂₂N₂O₃ 266.34

Benzeneacetamide, 4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]-;

2-{4-[2-Hydroxy-3-(isopropylamino)propoxy]-phenyl}acetamide

CAS RN®: 29122-68-7; UNII: 50VV3VW0TI.

1 DEFINITION

Atenolol contains NLT 98.0% and NMT 102.0% of atenolol (C₁₄H₂₂N₂O₃), calculated on the dried basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

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B. ▲The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.▲ (USP 1-May-2022)

3 ASSAY

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Procedure

Buffer: 3.4 g/L of potassium phosphate, monobasic, 1.25 g/L of octanesulfonic acid sodium salt, and 0.5 g/L of tetrabutylammonium hydrogen sulfate

0.8 M phosphoric acid solution: Dilute 5.2 mL of phosphoric acid in 100 mL of water.

Mobile phase: Methanol, tetrahydrofuran, and Buffer (18:2:80). Adjust with 0.8 M phosphoric acid solution to a pH of 3.0.

Standard solution: 0.01 mg/mL of USP Atenolol RS in Mobile phase. Sonication may be necessary for complete dissolution.

Sample solution: 0.01 mg/mL of Atenolol in Mobile phase. Sonication may be necessary for complete dissolution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 226 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 2 times the retention time of atenolol

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%▲ (USP 1-May-2022)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of atenolol (C₁₄H₂₂N₂O₃) in the portion of Atenolol taken:

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

r_U = peak response of atenolol from the Sample solution

r_S = peak response of atenolol from the Standard solution

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

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

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%

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Chloride and Sulfate 〈221〉, Chloride

Standard solution: 1.4 mL of 0.020 N hydrochloric acid in 100 mL of 0.15 N nitric acid▲ (USP 1-May-2022)

Sample solution: 1.0 g in 100 mL of 0.15 N nitric acid

Acceptance criteria: The Sample solution shows no more turbidity with 1 mL of silver nitrate TS than the Standard solution▲ (USP 1-May-2022) (0.1%).

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Organic Impurities

Buffer and Mobile phase: Prepare as directed in the Assay.

Impurity stock solutions 1–3: 0.1 mg/mL each of USP Atenolol Related Compound A RS, USP Atenolol Related Compound B RS, and USP Atenolol Related Compound F RS prepared as follows. Separately transfer an appropriate quantity of USP Atenolol Related Compound A RS, USP Atenolol Related Compound B RS, and USP Atenolol Related Compound F RS to individual suitable volumetric flasks. Add methanol to 10% of the final volume and sonicate to dissolve. Dilute with Mobile phase to volume.

Impurity stock solution 4: 0.1 mg/mL of USP Atenolol Related Compound E RS prepared as follows. Transfer an appropriate quantity of USP Atenolol Related Compound E RS to a suitable volumetric flask. Add acetonitrile to 50% of the final volume and sonicate to dissolve. Dilute with water to volume.

Sensitivity solution: 0.5 μg/mL of USP Atenolol RS in Mobile phase

Standard solution: 0.01 mg/mL of USP Atenolol RS and 0.005 mg/mL each of USP Atenolol Related Compound A RS, USP Atenolol Related Compound B RS, USP Atenolol Related Compound E RS, and USP Atenolol Related Compound F RS from the corresponding Impurity stock solution in Mobile phase

Sample solution: 2 mg/mL of Atenolol in Mobile phase prepared as follows. Transfer a suitable amount of Atenolol to a suitable volumetric flask. Add Mobile phase to 50% of the final volume and sonicate to dissolve. Dilute with Mobile phase to volume.

Chromatographic system: Proceed as directed in the Assay, except for the Run time.

Run time: NLT 5 times the retention time of atenolol

System suitability

Samples: Sensitivity solution and Standard solution

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

Suitability requirements

Resolution: NLT 2.0 between atenolol related compound B and atenolol related compound A, Standard solution

Relative standard deviation: NMT 2.0% for atenolol and NMT 5.0% each for atenolol related compounds A, B, E, and F, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of atenolol related compounds A, B, E, and F in the portion of Atenolol taken:

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

r_U = peak response of atenolol related compound A, B, E, or F from the Sample solution

r_S = peak response of atenolol related compound A, B, E, or F from the Standard solution

C_S = concentration of the corresponding Reference Standard in the Standard solution (mg/mL)

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

Calculate the percentage of atenolol related compound G and any unspecified impurity in the portion of Atenolol taken:

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

r_U = peak response of atenolol related compound G or any unspecified impurity from the Sample solution

r_S = peak response of atenolol from the Standard solution

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

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

F = relative response factor for atenolol related compound G or any unspecified impurity (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.025%.

ᵃ For quantification purposes, integrate the doublet peaks of atenolol related compound F.

ᵇ 2-{4-[2-Hydroxy-3-(isopropylamino)propoxy]phenyl}acetic acid.

5 SPECIFIC TESTS

Delete the following:

Melting Range or Temperature, Class I〈741〉: 152°–156.5°▲ (USP 1-May-2022)

Loss on Drying 〈731〉

Analysis: Dry at 105° to constant weight.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

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Packaging and Storage: Preserve in well-closed containers. Store at controlled (USP 1-May-2022) room temperature.

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USP Reference Standards 〈11〉

USP Atenolol RS

USP Atenolol Related Compound A RS

2-(4-Hydroxyphenyl)acetamide.

C₈H₉NO₂ 151.17

USP Atenolol Related Compound B RS

2-[4-(2,3-Dihydroxypropoxy)phenyl]acetamide.

C₁₁H₁₅NO₄ 225.24

USP Atenolol Related Compound E RS

2,2'-{[(2-Hydroxypropane-1,3-diyl)bis(oxy)]bis(4,1-phenylene)}diacetamide.

C₁₉H₂₂N₂O₅ 358.39

USP Atenolol Related Compound F RS

2,2'-[{[(Isopropylazanediyl)bis(2-hydroxypropane-3,1-diyl)]bis(oxy)}bis(4,1-phenylene)]diacetamide.

C₂₅H₃₅N₃O₆ 473.57▲ (USP 1-May-2022)