Penicillin G Potassium

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

C₁₆H₁₇KN₂O₄S 372.48

4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 3,3-dimethyl-7-oxo-6-[(phenylacetyl)amino]-, monopotassium salt, [2S-(2α,5α,6β)]-;

Monopotassium (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate CAS RN®: 113-98-4;

UNII: VL775ZTH4C.

1 DEFINITION

Penicillin G Potassium has a potency of NLT 1440 and NMT 1680 Penicillin G Units/mg.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (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.

C.

Diluent: Glycerin and water (25:14)

Solution A: 106 mg/mL of sodium carbonate in water

Solution B: 120 mg/mL of sodium sulfide in Diluent, prepared as follows. Dissolve sodium sulfide in Diluent, using about 45% of the final volume and heat. Allow to cool, and dilute with Diluent to the final volume.

Solution C: 150 mg/mL of tartaric acid in water

Sample solution: 0.1 g of Penicillin G Potassium in 2 mL of water

Analysis

Part 1: Add 1 mL of Solution A to the Sample solution and heat.

Part 2: To the hot solution from Part 1 add 0.05 mL of Solution B.

Part 3: Cool the mixture from Part 2 in iced water and add 2 mL of Solution C. Allow to stand.

Acceptance criteria: Meets the requirements for Parts 1, 2, and 3

Part 1: No precipitate is formed.

Part 2: No precipitate is formed.

Part 3: A white precipitate is formed.

3 ASSAY

Procedure

Solution A: 0.01 M monobasic potassium phosphate

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

System suitability solution: 0.1 mg/mL each of USP Penicillin G Potassium RS and 2-phenylacetamide in water

Standard solution: 0.1 mg/mL of USP Penicillin G Potassium RS in water. This solution contains about 160 Penicillin G Units/mL. Shake as needed to dissolve.

Sample solution: 0.1 mg/mL of Penicillin G Potassium in water. Shake as needed to dissolve.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 10-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 10 μL

System suitability

Samples: System suitability solution and Standard solution

[Note - The relative retention times for 2-phenylacetamide and penicillin G are about 0.8 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between 2-phenylacetamide and penicillin G, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the potency of penicillin G potassium, in Penicillin G Units/mg, in the portion of Penicillin G Potassium taken:

Result = (r_U/r_S) × (C_S/C_U) × P

r_U = peak response of penicillin G from the Sample solution

r_S = peak response of penicillin G from the Standard solution

C_S = concentration of USP Penicillin G Potassium RS in the Standard solution (mg/mL)

C_U = concentration of Penicillin G Potassium in the Sample solution (mg/mL)

P = potency of USP Penicillin G Potassium RS (Penicillin G Units/mg)

Acceptance criteria: 1440–1680 Penicillin G Units/mg

4 SPECIFIC TESTS

Crystallinity 〈695〉: Meets the requirements

pH 〈791〉

Sample solution: 60 mg/mL of Penicillin G Potassium in water

Acceptance criteria: 5.0–7.5

Loss on Drying 〈731〉

Sample: 100 mg of Penicillin G Potassium

Analysis: Dry the Sample in a capillary-stoppered bottle under vacuum at 60° for 3 h.

Acceptance criteria: NMT 1.5%

Bacterial Endotoxins Test 〈85〉: Where the label states that Penicillin G Potassium is sterile or it must be subjected to further processing during the preparation of injectable dosage forms, it has NMT 0.01 USP Endotoxin Units/100 Penicillin G Units.

Sterility Tests 〈71〉: Where the label states that Penicillin G Potassium is sterile, it meets the requirements.

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

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.

USP Reference Standards 〈11〉

USP Penicillin G Potassium RS