Meropenem for Injection

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

Meropenem for Injection is a sterile dry mixture of Meropenem and Sodium Carbonate. It contains NLT 90.0% and NMT 120.0% of the labeled amount of meropenem (C₁₇H₂₅N₃O₅S).

2 IDENTIFICATION

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

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

Procedure

Buffer: Dilute 15 mL of tetrabutylammonium hydroxide solution (25% in water) with water to 750 mL. Adjust with 10% phosphoric acid TS to a pH of 7.5 ± 0.1.

Mobile phase: Acetonitrile, methanol, and Buffer (ERR 1-Feb-2020) (150:100:750)

Standard solution: 0.11 mg/mL of USP Meropenem RS in Mobile phase. Immediately after preparation, store this solution in a refrigerator, and use within 24 h.

Sample stock solution 1 (where it is represented as being a single-dose container): Nominally 1 mg/mL of meropenem, prepared as follows. Constitute a container of Meropenem for Injection with a volume of water, corresponding to the quantity of solvent specified in the labeling. Withdraw all of the withdrawable contents, using a suitable hypodermic needle and syringe, and transfer to a suitable volumetric flask. Dilute with water to volume, and mix.

Sample solution 1: Nominally 0.1 mg/mL of meropenem in Mobile phase from Sample stock solution 1. Hold this Sample solution 1 for 2 h at 25 ± 1° before testing.

Sample stock solution 2 (where the label states the quantity of meropenem in a given volume of constituted solution): Nominally 1 mg/mL of meropenem, prepared as follows. Constitute a container of Meropenem for Injection with a volume of water corresponding to the quantity of solvent specified in the labeling, and dilute with water.

Sample solution 2: Nominally 0.1 mg/mL of meropenem in Mobile phase from Sample stock solution 2. Hold this Sample solution 2 for 2 h at 25 ± 1° before testing.

Chromatographic system

(See Chromatography 〈621〉, System Suitability)

Mode: LC

Detector: UV 300 nm. For Identi

cation B, use a diode array detector in the range of 200–400 nm.

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution 1 or Sample solution 2

Calculate the percentage of the labeled amount of meropenem (C₁₇H₂₅N₃O₅S) in the portion of Meropenem for Injection taken:

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

r_U = peak response of meropenem from Sample solution 1 or Sample solution 2

r_S = peak response of meropenem from the Standard solution

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

C_U = nominal concentration of meropenem in Sample solution 1 or Sample solution 2 (mg/mL)

P = potency of meropenem in USP Meropenem RS (mg/mg)

Acceptance criteria: 90.0%–120.0%

4 OTHER COMPONENTS

Content of Sodium

Solution A: 38.1 g/L of potassium chloride in water

Standard stock solution: 25.42 μg/mL of sodium chloride (previously dried at 105° for 2 h) in water

Standard solution: 2.5 μg/mL of sodium chloride from the Standard stock solution mixed first with Solution A to 10% of the final volume and diluted with water to volume

Sample stock solution 1 (where it is represented as being a single-dose container): Nominally 0.125 mg/mL of meropenem, prepared as follows. Constitute a container of Meropenem for Injection with a volume of water corresponding to the quantity of solvent specified in the labeling. Withdraw all of the withdrawable contents, using a suitable hypodermic needle and syringe, and transfer to a suitable volumetric flask. Dilute with water to volume.

Sample stock solution 2 (where the label states the quantity of meropenem in a given volume of constituted solution): Nominally 0.125 mg/mL of meropenem, prepared as follows. Constitute a container of Meropenem for Injection with a volume of water, corresponding to the quantity of solvent specified in the labeling. Transfer the constituted solution to a suitable volumetric flask, and dilute with water to volume.

Sample solution: Nominally 0.0125 mg/mL of meropenem from Sample stock solution 1 or Sample stock solution 2 mixed first with Solution A to 10% of the final volume, and dilute with water to volume

Blank: Solution A and water (1:10)

Instrumental conditions

(See Atomic Absorption Spectroscopy 〈852〉.)

Mode: Atomic absorption spectroscopy

Analytical wavelength: 589.6 nm sodium emission line

Burner: Single-slot

Flame: Air–acetylene

Lamp: Sodium hollow-cathode

Analysis

Samples: Standard solution, Sample solution, and Blank

Calculate the percentage of sodium (Na) in the portion of Meropenem for Injection taken:

Result = (A_U/A_S) × (C_S/C_U) × (M_r1/M_r2) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

C_S = concentration of sodium chloride in the Standard solution (μg/mL)

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

M_r1 = atomic weight of sodium, 22.99

M_r2 = molecular weight of sodium chloride, 58.44

Acceptance criteria: 80%–120% of the labeled amount of sodium

5 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements

6 IMPURITIES

Organic Impurities

Buffer: Mix 1.0 mL of triethylamine and 900 mL of water. Adjust with 10% phosphoric acid TS to a pH of 5.0 ± 0.1, and dilute with water to 1000 mL.

Mobile phase: Acetonitrile and Buffer (70:1000)

Peak identification solution: 5 mg/mL of USP Meropenem RS in Mobile phase. Use this solution between 1 and 24 h from preparation.

Standard solution: 0.029 mg/mL of USP Meropenem RS in Buffer. Store this solution in a refrigerator immediately after preparation, and use within 24 h.

Sample solution: Nominally prepare 5 mg/mL of meropenem in Buffer from Meropenem for Injection. This solution has to be prepared fresh and used immediately.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Column temperature: 40°

Flow rate: 1.6 mL/min

Injection volume: 10 μL

Run time: NLT 3 times the retention time of meropenem

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Peak identi

cation solution, Standard solution, and Sample solution

Chromatograph the Peak identification solution and identify the components on the basis of their relative retention times, as shown in

Table 1.

Calculate the percentage of each individual impurity in the portion of Meropenem for Injection taken:

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

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

r_S = peak response of meropenem from the Standard solution

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

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

P = potency of meropenem in USP Meropenem RS (mg/mg)

Acceptance criteria: See Table 1.

Table 1

^a (4R,5S)-5-[(1S,2R)-1-Carboxy-2-hydroxypropyl]-3-{[(3S,5S)-5-(dimethylcarbamoyl]pyrrolidin-3-yl]thio}-4-methyl-4,5-dihydro-1H-pyrrole-2-carboxylic acid.

^b (4R,5S,6S)-3-{[(3S,5S)-1-{(2S,3R)-2-[(2S,3R)-5-Carboxy-4-{[(3S,5S)-5-(dimethylcarbamoyl]pyrrolidin-3-yl]thio}-3-methyl-2,3-dihydro-1H-pyrrol-2-yl]-3-hydroxybutanoyl}-5-(dimethylcarbamoyl)pyrrolidin-3-yl]thio}-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid.

7 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: Meets the requirements

Constituted Solution: At the time of use, it meets the requirements for Injections and Implanted Drug Products 〈1〉, Product Quality Tests

Common to Parenteral Dosage Forms, Specific Tests, Completeness and clarity of solutions

Loss on Drying 〈731〉

Analysis: Dry under vacuum at 65° for 6 h.

Acceptance criteria: 9.0%–12.0%

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections

pH 〈791〉

Sample solution: 50 mg/mL

Acceptance criteria: 7.3–8.3

Sterility Tests 〈71〉: Meets the requirements

8 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers as described in Packaging and Storage Requirements 〈659〉, Injection Packaging, Packaging for Constitution. Store at controlled room temperature.

Labeling: Meets the requirements for Labeling 〈7〉, Labels and Labeling for Injectable Products. Label it to state the quantity, in mg, of sodium (Na) in a given dosage of meropenem.

USP Reference Standards 〈11〉

USP Meropenem RS