Metoprolol Tartrate 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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1 DEFINITION

Metoprolol Tartrate Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of metoprolol tartrate [(C₁₅H₂₅NO₃)₂ · C₄H₆O₆].

2 IDENTIFICATION

A.

Standard solution: 0.1 mg/mL of USP Metoprolol Tartrate RS in water

Sample solution: Transfer an amount equivalent to 50 mg of metoprolol tartrate from a quantity of finely powdered Tablets to a 500-mL volumetric flask, dilute with water to volume, and mix. Pass a portion of the solution through a filter of 1-µm or finer pore size.

Acceptance criteria: The UV spectrum of the Sample solution exhibits maxima and minima at the same wavelengths as those of the Standard solution.

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

3 ASSAY

PROCEDURE

Mobile phase: 961 mg of sodium 1-pentanesulfonate and 82 mg of anhydrous sodium acetate in a mixture of 550 mL of methanol and 470 mL of water. Add 0.57 mL of glacial acetic acid.

Diluent: Methanol and 0.1 N hydrochloric acid (1:1)

System suitability stock solution: 0.72 mg/mL of USP Oxprenolol Hydrochloride RS in Diluent

Standard stock solution: 1 mg/mL of USP Metoprolol Tartrate RS in Diluent

System suitability solution: System suitability stock solution and Standard stock solution (1:1)

Standard solution: 0.5 mg/mL of USP Metoprolol Tartrate RS from the Standard stock solution in Mobile phase

Sample stock solution: Nominally 1 mg/mL of metoprolol tartrate from Tablets prepared as follows. Transfer a portion of finely powdered Tablets (NLT 20), equivalent to about 50 mg of metoprolol tartrate, to a 50-ml volumetric flask, add 30 mL of Diluent, shake by mechanical means for 30 min, sonicate for 15 min, and heat on a steam bath for 10 min. Allow the solution to cool to room temperature, dilute with Diluent to volume, and centrifuge a portion of the solution. Use the supernatant.

Sample solution: Nominally 0.5 mg/mL of metoprolol tartrate prepared from the Sample stock solution in Mobile phase. Pass a portion of the solution through a filter of 0.5-µm or finer pore size. Discard the first few milliliters of the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm x 30-cm; 10-µm packing 11

Flow rate: 1 mL/min

Injection volume: 30 µL

System suitability

Samples: Standard solution and System suitability solution

[NOTE-The relative retention times for metoprolol and oxprenolol are 0.8 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between metoprolol and oxprenolol, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of metoprolol tartrate [(C₁₅H₂₅NO₃)₂ · C₄H₆O₆] in the portion of Tablets taken:

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

r_U = peak response of metoprolol from the Sample solution

r_S = peak response of metoprolol from the Standard solution

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

C_U = nominal concentration of metoprolol tartrate in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Medium: Simulated gastric fluid TS (without enzyme); 900 mL

Apparatus 1: 100 rpm

Time: 30 min

Standard solution: USP Metoprolol Tartrate RS with a known concentration in Medium

Sample solution: Sample per the chapter. Dilute with Medium as needed.

Instrumental conditions

Mode: UV

Analytical wavelength: 275 nm

Analysis

Samples: Standard solution and Sample solution

Tolerances: NLT 75% (Q) of the labeled amount of metoprolol tartrate [(C₁₅H₂₅NO₃)₂ · C₄H₆O₆] is dissolved. 

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Solution A: 3.9 g of ammonium acetate in 810 mL of water. Add 2.0 mL of triethylamine, 10.0 mL of glacial acetic acid, and 3.0 mL of phosphoric acid. [NOTE-Adjust the pH of the solution to 3.7 if needed.]

Solution B: Acetonitrile and Solution A (70:30)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and Solution A (17:83)

System suitability solution: 0.01 mg/mL each of tyrosol and USP Metoprolol Related Compound C RS in Diluent

Standard solution: 0.01 mg/mL of USP Metoprolol Tartrate RS in Diluent

Sensitivity solution: 0.7 µg/mL of USP Metoprolol Tartrate RS from the Standard solution in Diluent

Sample solution: Nominally 1 mg/mL of metoprolol tartrate from Tablets prepared as follows. Transfer 100 mg of metoprolol tartrate from a quantity of finely powdered Tablets (NLT 20) to a 100-mL volumetric flask, and add 50 mL of Diluent. Sonication and stirring may be necessary for complete dissolution. Dilute with Diluent to volume. Centrifuge a portion of the solution. Use the supernatant.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 275 nm

Column: 4.6-mm x 15-cm; 5-µm packing 11

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements

Resolution: NLT 1.5 between tyrosol and metoprolol related compound C, 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 each unspecified degradation product in the portion of Tablets taken:

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

r_U = peak response of each unspecified degradation product from the Sample solution

r_S = peak response of metoprolol from the Standard solution s

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

C_U = nominal concentration of metoprolol tartrate in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. Disregard peaks below 0.1%.

Table 2

^a 2-(4-Hydroxyphenyl)ethanol. For resolution measurement only.

^b Specified impurities controlled in the drug substance.

^c (+)-1-(Ethylamino)-3-[4-(2-methoxyethyl)phenoxy]-propan-2-ol.

^d (+)-N,N-Bis-[2-hydroxy-3-[4-(2-methoxyethyl)phenoxypropyl] (1-methylethyl)amine hydrochloride. It has two diastereomers.

^e (+)-1-Chloro-2-hydroxy-3-[4-(2-methoxyethyl)phenoxy]-propane.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers. Store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Metoprolol Related Compound C RS

4-[2-Hydroxy-3-(isopropylamino)propoxy]benzaldehyde hydrochloride.

C₁₃H₁₉NO₃ · HCl            273.76

USP Metoprolol Tartrate RS

USP Oxprenolol Hydrochloride RS