Piperacillin 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)

DOWNLOAD PDF HERE

1 DEFINITION

Piperacillin for Injection contains an amount of Piperacillin Sodium equivalent to NLT 90.0% and NMT 120.0% of the labeled amount of piperacillin (C₂₃H₂₇N₅O₇S).

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

Sample: Dissolve 250 mg in water. Add 0.5 mL of 2N hydrochloric acid and 5 mL of ethyl acetate. Stir, and allow to stand for 10 min in ice water. Pass through a suitable sintered-glass filter, applying suction. Wash the crystals with 5 mL of water and 5 mL of ethyl acetate, then dry in an oven at 60° for 60 min.

Acceptance criteria: Meets the requirements

3 ASSAY

3.1 PROCEDURE

Mobile phase: Methanol, 0.2 M monobasic sodium phosphate, 0.4 M tetrabutylammonium hydroxide, and water (450:100:3:447). Adjust with phosphoric acid to a pH of 5.50.

System suitability solution: 0.1 mg/mL of USP Ampicillin RS and 0.2 mg/mL of USP Piperacillin RS in Mobile phase

Standard solution: 0.4 mg/mL of USP Piperacillin RS in Mobile phase. Dissolve in a few drops of methanol, and dilute with Mobile phase to volume. Use this solution within 1 h.

Sample solution 1 (where it is labeled for use as a single-dose container): Equivalent to 0.4 mg/mL of piperacillin from Piperacillin for Injection constituted as directed below.

Constitute Piperacillin for Injection in a volume of water corresponding to the volume of solvent specified in the labeling. Withdraw all of the withdrawable contents using a suitable hypodermic needle and syringe, and dilute with Mobile phase.

Sample solution 2 (where the label states the quantity of piperacillin in a given volume of the constituted solution): Equivalent to 0.4 mg/mL of piperacillin from Piperacillin for Injection constituted as directed below.

Constitute Piperacillin for Injection in a volume of water corresponding to the volume of solvent specified in the labeling. Dilute an aliquot of the constituted solution with Mobile phase.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

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

Flow rate: 1 mL/min

Injection volume: 10 µL

3.3 System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 16 between ampicillin and piperacillin, System suitability solution

Tailing factor: NMT 1.2 for the piperacillin peak, System suitability solution

Relative standard deviation: NMT 2%, Standard solution

3.4 Analysis

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

Calculate the percentage of the labeled amount of piperacillin (C₂₃H₂₇N₅O₇S) in the container or in the portion of constituted solution taken:

Result = (r_U/r_S) x (C_S/C_U) x P x F x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

P = potency of piperacillin in USP Piperacillin RS (µg/mg)

F = conversion factor, 0.001 mg/µg

Acceptance criteria: 90.0%-120.0%

4 PERFORMANCE TESTS

UNIFORMITY OF DOSAGE UNITS (905): Meets the requirements

5 IMPURITIES

ORGANIC IMPURITIES

Mobile phase, System suitability solution, Sample solution 1, Sample solution 2, Chromatographic system, and System suitability: Proceed as directed in the Assay. Evaluate the Relative standard deviation using the Standard solution prepared in the Assay.

Standard solution: 40 µg/mL of USP Piperacillin RS in Mobile phase. Dissolve in a few drops of methanol, and dilute with Mobile phase to volume. Use this solution within 1 h.

Analysis

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

Calculate the percentage of piperacillin penicilloic acid and acetylated penicilloic acid of piperacillin in the portion of Piperacillin for Injection taken:

Result = (r_U/r_S) x (C_S/C_U) x P x (1/F₁) x F₂ x 100

r_U = peak response of piperacillin penicilloic acid or acetylated penicilloic acid of piperacillin from Sample solution 1 or Sample solution 2

r_S = peak response of piperacillin from the Standard solution

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

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

P = potency of piperacillin in USP Piperacillin RS (µg/mg)

F₁ = relative response factor (see Table 1)

F₂ = conversion factor, 0.001 mg/µg

Acceptance criteria: See Table 1.

Table 1

^a These are process impurities that are listed here for information only; they are controlled in the drug substance and are not to be reported.

^b 1-Ethyl-2,3-piperazinedione.

^c (2R,4S)-3-Acetyl-2-{(1R)-carboxy[2-(4-ethyl-2,3-dioxopiperazine-1-carboxamido)-2-phenylacetamido]methyl}-5,5-dimethylthiazolidine-4-carboxylic acid.

^d (2R,4S)-2-{(1R)-Carboxy[2-(4-ethyl-2,3-dioxopiperazine-1-carboxamido)-2-phenylacetamido]methyl}-5,5-dimethylthiazolidine-4-carboxylic acid.

6 SPECIFIC TESTS

6.1 CONSTITUTED SOLUTION

At the time of use, it meets the requirements in Injections and Implanted Drug Products (1), Specific Tests, Completeness and clarity of solutions.

6.2 BACTERIAL ENDOTOXINS TEST (85)

It contains NMT 0.07 USP Endotoxin Unit/mg of piperacillin.

6.3 STERILITY TESTS (71)

It meets the requirements when tested as directed in Test for Sterility of the Product to Be Examined, Membrane Filtration.

6.4 PH (791)

4.8-6.8, in a solution of 200 mg/mL of piperacillin

6.5 WATER DETERMINATION, Method I (921)

NMT 0.9%

6.6 PARTICULATE MATTER IN INJECTIONS (788)

Meets the requirements for small-volume injections

6.7 OTHER REQUIREMENTS

It meets the requirements in Labeling_(7), Labels and Labeling for Injectable Products.

7 ADDITIONAL REQUIREMENTS

7.1 PACKAGING AND STORAGE

Preserve as described in Packaging and Storage Requirements (659), Injection Packaging, Packaging for constitution.

7.2 USP REFERENCE STANDARDS (11)

USP Ampicillin RS

USP Piperacillin RS