Penicillin V Potassium

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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C₁₆H₁₇KN₂O₅S           388.48

4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 3,3-dimethyl-7-oxo-6-[(phenoxyacetyl)amino]-, monopotassium salt, [2S-(2α,5α,6β)]-; Monopotassium (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate  CAS RN®: 132-98-9; UNII:146T0TU1JB.

1 DEFINITION

Penicillin V Potassium has a potency of NLT 1380 and NMT 1610 Penicillin V 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 penicillin V 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 nal volume and heat. Allow to cool, and dilute with Diluent to the nal volume.

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

Sample solution: 0.1 g of Penicillin V 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

Mobile phase: Acetonitrile, glacial acetic acid, and water (350:5.75:650)

System suitability solution: 2.5 mg/mL each of USP Penicillin G Potassium RS and USP Penicillin V Potassium RS in Mobile phase Standard solution: 2.5 mg/mL of USP Penicillin V Potassium RS in Mobile phase

Sample solution: 2.5 mg/mL of Penicillin V Potassium in Mobile phase

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm × 30-cm; 10-µm packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

3.2 System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for p-hydroxypenicillin V, penicillin G, and penicillin V are about 0.4, 0.8, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between penicillin G and penicillin V, System suitability solution

Relative standard deviation: NMT 1.0%, Standard solution

3.3 Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U /r_S) × (C_S /C_U ) × P

r_U = sum of the p-hydroxypenicillin V and penicillin V peak responses from the Sample solution

r_S = sum of the p-hydroxypenicillin V and penicillin V peak responses from the Standard solution

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

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

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

Acceptance criteria: 1380–1610 Penicillin V Units/mg

4 IMPURITIES

4.1 Limit of Phenoxyacetic Acid

Mobile phase: Acetonitrile, glacial acetic acid, and water (35:1:65)

Diluent: pH 6.6 phosphate buffer (see Reagents, Indicators, and Solutions—Buffer Solutions)

Standard solution: 0.1 mg/mL of phenoxyacetic acid in Diluent

Sample solution: 20 mg/mL of Penicillin V Potassium in Diluent. Use this solution on the day prepared.

4.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

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

Flow rate: 1 mL/min

Injection volume: 20 µL

4.1.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

4.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of phenoxyacetic acid in the portion of Penicillin V Potassium taken:

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

r_U = phenoxyacetic acid peak response from the Sample solution

r_S = phenoxyacetic acid peak response from the Standard solution

C_S = concentration of phenoxyacetic acid in the Standard solution (mg/mL)

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

Acceptance criteria: NMT 0.5%

4.2 Limit of p-Hydroxypenicillin V

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

Analysis

Sample: Sample solution

Calculate the percentage of p-hydroxypenicillin V in the portion of Penicillin V Potassium taken:

Result = (r_U /r_T ) × 100

r_U = p-hydroxypenicillin V peak response from the Sample solution

r_T = sum of the p-hydroxypenicillin V and penicillin V peak responses from the Sample solution

Acceptance criteria: NMT 5.0%

5 SPECIFIC TESTS

Optical Rotation 〈781S〉, Specific Rotation

Sample solution: 10 mg/mL of Penicillin V Potassium in carbon dioxide-free water

Acceptance criteria: +220° to +235°

Crystallinity 〈695〉: Meets the requirements

pH 〈791〉

Sample solution: 30 mg/mL of Penicillin V Potassium in water

Acceptance criteria: 4.0–7.5

Loss on Drying 〈731〉

Sample: 100 mg of Penicillin V Potassium

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

Acceptance criteria: NMT 1.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

Labeling: Label it to indicate that it is to be used in the manufacture of nonparenteral drugs only.

USP Reference Standards 〈11〉

USP Penicillin G Potassium RS

USP Penicillin V Potassium RS