Piperacillin and Tazobactam for Injection
DEFINITION
Piperacillin and Tazobactam for Injection contains amounts of Piperacillin Sodium and Tazobactam Sodium equivalent to NLT 90.0% and NMT 110.0% of the labeled amounts of piperacillin (C23H27N5O7S) and tazobactam (C10H12N4O5S), the labeled amounts representing proportions of piperacillin to tazobactam of 8:1. It may contain small amounts of a suitable buffer and stabilizer.
IDENTIFICATION
• The retention times of the major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
[NoteRefrigerate the Standard solution and the Sample solution immediately after preparation and during analysis, using a refrigerated autosampler set at 5 ± 3. The solutions should be analyzed within 24 h of preparation. ]
Solution A:
Phosphoric acid and water (1:4)
Solution B:
Dilute the contents of one vial of tetrabutylammonium hydrogen sulfate ion pairing reagent with water to 1 L.
Mobile phase:
Acetonitrile and Solution B (1:3), adjusted with Solution A to a pH of 3.8
Diluent:
Acetonitrile and water (1:3)
Standard stock solution A:
0.06 mg/mL of USP Tazobactam Related Compound A RS in Diluent
Standard stock solution B:
0.5 mg/mL of USP Tazobactam RS in Diluent
Standard stock solution C:
1.0 mg/mL of USP Piperacillin RS in acetonitrile and Diluent (1:24). [NoteDissolve first in acetonitrile, using about 4% of the final volume, and dilute with Diluent to volume. ]
System suitability solution:
0.006 mg/mL of tazobactam related compound A from Standard stock solution A and 0.025 mg/mL of tazobactam from Standard stock solution B in Diluent
Standard solution:
0.025 mg/mL of tazobactam from Standard stock solution B and 0.2 mg/mL of piperacillin from Standard stock solution C in Mobile phase
Sample solution:
Equivalent to 0.025 mg/mL of tazobactam and 0.2 mg/mL of piperacillin from Piperacillin and Tazobactam for Injection in Mobile phase
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 15-cm; 3-µm packing L11
Autosampler temperature:
5 ± 3
Flow rate:
1 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 3 between tazobactam related compound A and tazobactam, System suitability solution
Tailing factor:
NMT 1.8 for tazobactam and piperacillin, Standard solution
Relative standard deviation:
NMT 2% for tazobactam and piperacillin, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentages of C23H27N5O7S and C10H12N4O5S in the portion of Piperacillin and Tazobactam for Injection taken:
Result = (rU/rS) × (CS/CU) × P × 100
Acceptance criteria:
90.0%110.0%
PERFORMANCE TESTS
• Uniformity of Dosage Units 905:
Meets the requirements
IMPURITIES
Organic Impurities
• Procedure
[NoteRefrigerate the Standard solution and the Sample solution immediately after preparation and during analysis, using a refrigerated autosampler set at 5 ± 3. The solutions should be analyzed within 24 h of preparation. ]
Mobile phase, Diluent, System suitability solution, Standard solution, Sample solution, Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Piperacillin and Tazobactam for Injection taken:
Result = (rU/rS) × (CS/WU) × P × D × (1/F) × 100
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 5.0%. [NoteTotal impurities does not include piperacillin related compound A. ]
Impurity Table 1
SPECIFIC TESTS
• Bacterial Endotoxins Test 85:
It contains NMT 0.08 USP Endotoxin Unit in a portion equivalent to 1 mg of a mixture of piperacillin and tazobactam (0.89 and 0.11 mg, respectively).
• Sterility Tests 71:
Meets the requirements
• Particulate Matter in Injections 788:
Meets the requirements
• pH 791:
5.07.0, in a solution containing the equivalent of 40 mg/mL of piperacillin
• Water Determination, Method I 921:
NMT 2.5%
• Other Requirements:
It meets the requirements under Injections 1.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve as described in Containers for Sterile Solids under Injections 1, Packaging. Store at controlled room temperature.
• Labeling:
Label it to indicate its sodium content.
• USP Reference Standards 11
USP Endotoxin RS
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 4335
Pharmacopeial Forum: Volume No. 37(2)
|