Metoprolol Tartrate

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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[(C₁₅H₂₅NO₃)₂ · C₄H₆O₆]          684.81

2-Propanol, 1-[4-(2-methoxyethyl)phenoxy)-3-[(1-methylethyl)amino]-, (±), [R-(R*,R*)]-2,3-dihydroxy butanedioate (2:1) (salt);

^▲(+)-1-(Isopropylamino)-3-[p-(2-methoxyethyl)phenoxy]-2-propanol (+)-tartrate (2:1) (salt);

1-(Isopropylamino)-3-[4-(2-methoxyethyl)phenoxy)propan-2-ol L-tartrate _{▲(ERR 1-Dec-2018)} CAS RN^®: 56392-17-7; UNII: W5S57Y3A5L.

1 DEFINITION

Metoprolol Tartrate contains NLT 98.0% and NMT 102.0% of metoprolol tartrate [(C₁₅H₂₅NO₃)₂ · C₄H₆O₆], calculated on the dried basis. 

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197M _{▲(CN 1-May-2020)}

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

[NOTE-Use all solutions within 48 h.]

Buffer: 1.3 g/L of sodium dodecyl sulfate in 0.1% (w/v) phosphoric acid

Mobile phase: Acetonitrile and Buffer (400:600)

Standard solution: 1 mg/mL of USP Metoprolol Tartrate RS in Mobile phase

Sample solution: 1 mg/mL of Metoprolol Tartrate in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 223 nm

Column: 4.6-mm x 15-cm; 5-µm packing L7

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of metoprolol tartrate [(C₁₅H₂₅NO₃)₂ · C₄H₆O₆], in the portion of sample 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 = concentration of Metoprolol Tartrate in the Sample solution (mg/mL)

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

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

[NOTE-Use all solutions within 48 hrs.]

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

System suitability solution: 5 µg/mL each of USP Metoprolol Tartrate RS, USP Metoprolol Related Compound A RS, USP Metoprolol Related Compound B RS, and USP Metoprolol Related Compound C RS in Mobile phase

Standard solution: 1 µg/mL each of USP Metoprolol Tartrate RS. USP Metoprolol Related Compound A RS. USP Metoprolol Related Compound B RS, USP Metoprolol Related Compound C RS, and USP Metoprolol Related Compound D. RS in Mobile phase

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between metoprolol related compound A and metoprolol related compound B; NLT 2.5 between metoprolol related compound B and metoprolol related compound C, System suitability solution

Relative standard deviation: NMT 5.0% for the metoprolol peak, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of sample taken:

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

r_U = peak response of each individual impurity in the Sample solution

r_S = peak response of the corresponding metoprolol related compound or metoprolol (for calculating any individual unspecified impurity) in the Standard solution

C_S = concentration of the corresponding USP Metoprolol Related Compound RS or USP Metoprolol Tartrate RS (for calculating any individual unspecified impurity) in the Standard solution (mg/mL) Cs

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

Acceptance criteria: See Table 1.

Table 1

^a (±)-4-[2-Hydroxy-3-(1-isopropyl)aminopropoxy]benzaldehyde).

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

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

^d (±)-N,N-bis-[2-Hydroxy-3-[4-(2-methoxyethyl)phenoxy]propyl] (1-methylethyl)amine hydrochloride.

^e The sum of the peak responses of the two diastereomers is used to calculate the amount of metoprolol related compound D.

^f Disregard any peak due to tartaric acid at about RRT 0.17.

5 SPECIFIC TESTS

5.1 OPTICAL ROTATION, Specific Rotation (781S)

Sample solution: 20 mg/mL in water

Acceptance criteria: +6.5" to +10.5" (t = 20 deg)

5.2 PH (791)

Sample solution: 100 mg/mL of Metoprolol Tartrate in water

Acceptance criteria: 6.0-7.0

5.3 LOSS ON DRYING (731)

Sample solution: Dry a sample in a vacuum at 60° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

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

USP REFERENCE STANDARDS (11)

USP Metoprolol Tartrate RS

USP Metoprolol Related Compound A RS

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

C₁₄H₂₃NO₃          253.34

USP Metoprolol Related Compound B RS

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

C₁₂H₁₇CIO₃          244.71

USP Metoprolol Related Compound C.RS

(±)-4-[2-Hydroxy-3-(1-isopropyl)aminopropoxy]benzaldehyde.

C₁₃H19NO₃           237.29

USP Metoprolol Related Compound D RS

(+)-N,N-bis-[2-Hydroxy-3-[4-(2-methoxyethyl)phenoxy]propyl] (1-methylethyl)amine hydrochloride.

C₂₇H₄₂NO₆         512.08