Atenolol Tablets

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 Tablets

1 DEFINITION

Atenolol Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of atenolol (C₁₄H₂₂N₂O₃).

2 IDENTIFICATION

Change to read:

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

Change to read:

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

3 ASSAY

Change to read:

Procedure

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

Buffer: 1.1 g of sodium 1-heptanesulfonate; 0.71 g of sodium phosphate, dibasic, anhydrous; and 2 mL of dibutylamine in 700 mL of water. Adjust with 0.8 M phosphoric acid solution to a pH of 3.0.▲ (USP 1-May-2022)

Mobile phase: ▲Methanol and Buffer (30:70)▲ (USP 1-May-2022)

Standard solution: 0.01 mg/mL of USP Atenolol RS in Mobile phase

Sample solution: ▲Nominally 0.01 mg/mL of atenolol in Mobile phase prepared as follows. Transfer 10 Tablets to a 1000-mL volumetric flask. Add 500 mL of Mobile phase and sonicate for 15 min to disintegrate the Tablets. Dilute with Mobile phase to volume. Centrifuge a portion of the solution.▲ (USP 1-May-2022) Dilute a volume of the supernatant with Mobile phase to obtain a solution nominally containing 0.01 mg/mL of atenolol.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 226 nm. ▲For Identification A, use a diode array detector in the range of 190–400 nm.▲ (USP 1-May-2022)

Column: 3.9-mm × 30-cm; ▲4-µm▲ (USP 1-May-2022) packing L1

Flow rate: 0.6 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ▲the labeled amount of▲ (USP 1-May-2022) atenolol (C₁₄H₂₂N₂O₃) in ▲the portion of Tablets▲ (USP 1-May-2022) 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 = nominal concentration of atenolol in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

Atenolol-Tablets-ttt

PERFORMANCE TESTS

Change to read:

• Dissolution 〈711〉

Medium: 0.1 N acetate buffer, pH 4.6 [prepared by mixing 44.9 parts (v/v) of 0.1 N sodium acetate with 55.1 parts (v/v) of 0.1 N acetic acid solution, and adjust with either diluted sodium hydroxide or diluted acetic acid to a pH of 4.6]; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

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

Standard solution: 0.01 mg/mL of USP Atenolol RS in Mobile phase

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Quantitatively dilute a measured volume of the filtrate with Mobile phase to obtain a solution estimated to contain about 0.01 mg/mL of atenolol.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ▲the labeled amount of▲ (USP 1-May-2022) atenolol (C₁₄H₂₂N₂O₃) dissolved:

Result = (r_U / r_S) × C_S × V × D × (100/L)

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)

V = volume of Medium, 900 mL

D = dilution factor of the Sample solution

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of atenolol (C₁₄H₂₂N₂O₃) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

4 IMPURITIES

Organic Impurities

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.

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: 0.001 mg/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: Nominally 2 mg/mL of atenolol in Mobile phase prepared as follows. Transfer an appropriate quantity of atenolol from powdered Tablets (NLT 20) to a suitable volumetric flask. Add Mobile phase to 50% of the final volume and sonicate for 15 min to dissolve. Dilute with Mobile phase to volume. Pass through a suitable filter of 0.45-µm pore size and discard the first 5 mL of filtrate.

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 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 Tablets 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 = nominal 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 Tablets 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 = nominal 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 0.05%.

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 ADDITIONAL REQUIREMENTS

Change to read:

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

Change to read:

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)