Metoprolol Tartrate Injection

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

Metoprolol Tartrate Injection is a sterile solution of Metoprolol Tartrate in Water for Injection. It contains Sodium Chloride as a tonicity-adjusting agent. It contains NLT 90.0% and NMT 110.0% of the labeled amount of metoprolol tartrate [(C₁₅H₂₅NO₃)₂ · C₄H₆O₆]

2 IDENTIFICATION

Change to read:

A. ^▲The retention time of metoprolol of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay _{▲(USP 1-May-2019)}

Add the following:

^▲B. The UV-Vis spectrum of the major peak of the Diluted sample stock solution corresponds to that of the Diluted standard stock solution, as obtained in the Assay _{▲(USP 1-May-2019)}

3 ASSAY

Change to read:

PROCEDURE

Solution A: 9.0 mg/mL of sodium chloride in water

Mobile phase: 961 mg of 1-pentanesulfonic acid sodium salt (monohydrate) 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.

Internal standard solution: 0.72 mg/mL of USP Oxprenolol Hydrochloride RS in freshly prepared Mobile phase

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

Standard solution: Standard stock solution and Internal standard solution (1:1)

^▲Diluted standard stock solution: 0.1 mg/mL of USP Metoprolol Tartrate RS from Standard stock solution in Solution A _{▲(USP 1-May-2019)}

Sample stock solution: Nominally 1 mg/mL of metoprolol tartrate from Injection prepared as follows. Transfer an accurately measured volume of Injection, if necessary, into Solution A.

Sample solution: Sample stock solution and Internal standard solution (1:1)

^▲Diluted sample stock solution: Nominally 0.1 mg/mL of metoprolol tartrate from Sample stock solution in Solution A _{▲(USP 1-May-2019)}

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identification B, use a diode array detector in the range of 200-400 nm. _{▲(USP 1-May-2019)}

Column: 3.9-mm x 30-cm; 10-µm (USP 1-May-2019) Packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard 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

Relative standard deviation: NMT 2.0% from three replicate injections

Analysis

Samples: Standard solution, Diluted standard stock solution, (USP 1-May-2019) Sample solution, and Diluted sample stock solution. [NOTE-The Diluted standard stock solution and Diluted sample stock solution are used for Identification B.] _{▲(USP 1-May-2019)}

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

                         Result = (R_U/R_S) × (C_S/C_U) × 100

R_U = peak response ratio of metoprolol to oxprenolol from the Sample solution

R_S = peak response ratio of metoprolol to oxprenolol from the Standard solution

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

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

Acceptance criteria: 90.0%-110.0%

4 IMPURITIES

Add the following:

ORGANIC IMPURITIES

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

Solution B: 9.0 mg/mL of sodium chloride in water. [NOTE-This solution is only needed when sample dilution is required.]

Mobile phase: Acetonitrile and Solution A (40:60)

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: 2.5 µg/mL each of USP Metoprolol Tartrate RS and USP Metoprolol Related Compound C. RS in Mobile phase

Sample solution: Nominally 1 mg/mL of metoprolol tartrate from a volume of Injection. Transfer an accurately measured volume of Injection, if necessary, into Solution B.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 223 nm

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

Column temperature: 30°

Flow rate: 1 mL/min.

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for metoprolol and metoprolol related compounds are listed in Table 1.]

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 3% for metoprolol and metoprolol related compound C, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of metoprolol related compound C in the portion of Injection taken:

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

r_U = peak response of metoprolol related compound C from the Sample solution

r_S = peak response of metoprolol related compound C from the Standard solution

C_S = concentration of USP Metoprolol Related Compound C RS in the Standard solution (µg/mL)

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

Calculate the percentage of any unspecified degradation product in the portion of Injection 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 (µg/mL) S

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

Acceptance criteria: See Table 1.

Table 1

^a Specified impurities controlled in the drug substance. They are not to be included in the calculation of the total degradation products.

5 SPECIFIC TESTS

PH (791): 5.0-8.0

BACTERIAL ENDOTOXINS TEST (85): NMT 25.0 USP Endotoxin Units/mg of metoprolol tartrate

STERILITY TESTS (71), Test for Sterility of the Product to be Examined. Membrane Filtration: Meets the requirements

OTHER REQUIREMENTS: It meets the requirements in Injections and Implanted Drug Products (1).

6 ADDITIONAL REQUIREMENTS

Change to read:

PACKAGING AND STORAGE: Preserve in single-dose, light-resistant containers, preferably of Type I or Type II glass. ^▲Store at controlled room temperature. _{▲(USP 1-May-2019)}

Change to read:

USP REFERENCE STANDARDS (11)

USP Metoprolol Tartrate RS

^▲USP Metoprolol Related Compound A RS

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

C₁₄H₂₃NO₂          253.34

USP Metoprolol Related Compound B RS

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

C₁₂H₁₇CIO₃         244.71

USP Metoprolol Related Compound C RS

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

C₁₃H₁₉NO₃ · HCl       273.76_{▲(USP 1-May-2019)}

USP Oxprenolol Hydrochloride RS