Meropenem

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 contains NLT 98.0% and NMT 101.0% of meropenem (C₁₇H₂₅N₃O₅S), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

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B. 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-Dec-2019)

3 ASSAY

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Procedure

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

Mobile phase: Acetonitrile, methanol, and Solution A (150:100:750)

Standard solution: 0.1 mg/mL of USP Meropenem RS in Mobile phase. Immediately after preparation, store this solution in a refrigerator, and use within 24 h.

Sample solution: 0.1 mg/mL of Meropenem in Mobile phase. Immediately after preparation, store this solution in a refrigerator, and use within 8 h.

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 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of meropenem (C₁₇H₂₅N₃O₅S) in the portion of Meropenem taken:

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

r_U = peak response of meropenem 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 = concentration of Meropenem in the Sample solution (mg/mL)

P = designated potency of USP Meropenem RS (mg/mg)

(USP 1-Dec-2019)

Acceptance criteria: 98.0%–101.0% on the anhydrous basis

4 IMPURITIES

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Residue on Ignition 〈281〉

Analysis: Ignite at 500 ± 50° (USP 1-Dec-2019)

Acceptance criteria: NMT 0.1%

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Organic Impurities

Solution A: 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 Solution A (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.

(USP 1-Dec-2019)

Standard solution: 0.025 mg/mL of USP Meropenem RS in Solution A

Store this solution in a refrigerator and use within 24 h. (USP 1-Dec-2019)

Sample solution: 5 mg/mL of Meropenem in Solution A. Use this Sample solution 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

(USP 1-Dec-2019)

Injection volume: 10 μL

Run time: NLT 3 times the retention time of meropenem

System suitability

Sample: Standard solution

Suitability requirements

(USP 1-Dec-2019)

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Peak identification 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. (USP 1-Dec-2019)

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

Result = (r_U/r_S) × (C_S/C_U) × P× 100 _{(USP 1-Dec-2019)}

r_U = peak response of any 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 = concentration of Meropenem in the Sample solution (mg/mL)

P = potency of meropenem in USP Meropenem RS (mg/mg) (USP 1-Dec-2019)

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.

(USP 1-Dec-2019)

Delete the following:

Limit of Acetone

Internal standard solution: 0.05 μL/mL of ethyl acetate in dimethylformamide

Standard stock solution: 0.5 mg/mL of acetone in dimethylformamide

Standard solution: Combine 1.0 mL of Standard stock solution and 10.0 mL of Internal standard solution.

Sample solution: Dissolve 100 mg of Meropenem in 0.2 mL of dimethylformamide and 2.0 mL of Internal standard solution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 3-mm × 2-m column; support S2

Temperature

Column: 150°

Injection port: 170°

Carrier gas: Nitrogen

Flow rate: Adjusted so that the retention time for acetone is about 3 min

Injection volume: 2 μL

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of acetone in the portion of Meropenem taken:

Result = (W_A/5 × W_U) × (r_U/r_S)

W_A = weight of acetone in the Standard solution (mg)

W_U = weight of Meropenem in the Sample solution (mg)

r_U = peak area ratio of acetone to the internal standard from the Sample solution

r_S = peak area ratio of acetone to the internal standard from the Standard solution

Acceptance criteria: NMT 0.05% (USP 1-Dec-2019)

5 SPECIFIC TESTS

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Bacterial Endotoxins Test 〈85〉: Where the label states that Meropenem is sterile or that it must be subjected to further processing during the preparation of injectable dosage forms, the level of bacterial endotoxins is such that the requirement under the relevant dosage form monograph(s) in which Meropenem is used can be met. (USP 1-Dec-2019)

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 5 mg/mL in water

Acceptance criteria: −17° to −21°, at 20°

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pH 〈791〉

Sample solution: 10 mg/mL in water (USP 1-Dec-2019)

Acceptance criteria: 4.0–6.0

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Sterility Tests 〈71〉: Where the label states that Meropenem is sterile or that it must be subjected to further processing during the preparation of injectable dosage forms, it meets the requirements. (USP 1-Dec-2019)

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Water Determination 〈921〉, Method I, Method Ia (USP 1-Dec-2019) or Method Ic: 11.4%–13.4%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store the dry powder at controlled room temperature.

Change to read:

Labeling: Where it is intended for use in preparing injectable dosage forms, the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms, it is so labeled. Where Meropenem must be subjected to further processing during the preparation of injectable dosage forms to ensure acceptable levels of bacterial endotoxins, it is so labeled. (USP 1-Dec-2019)

USP Reference Standards 〈11〉

USP Meropenem RS