Tazobactam
C10H12N4O5S 300.29
4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 3-methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl)-, 4,4-dioxide, [2S-(2
,3
,5)]-;
(2S,3S,5R)-3-Methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 4,4-dioxide
[89786-04-9].
C10H12N4O5S·½H2O
309.30
[428863-55-2].(RB 1-May-2011)
921
:
NMT 0.6% for the anhydrous form; 2.2–3.8% for the hemihydrate form(RB 1-May-2011)
• Labeling:
Where it is the hemihydrate form, the label so indicates.(RB 1-May-2011)
(taz'' oh bak' tam).
Change to read:
+'&img=../../images/v35300/cas-89786-04-9.gif&casNumber=89786-04-9&usp=35&nf=30&chemicalStructureImage=true&ID='+parent.myID,600,500);)
C10H12N4O5S 300.29
4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 3-methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl)-, 4,4-dioxide, [2S-(2
,3,5)]-;
(2S,3S,5R)-3-Methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 4,4-dioxide
[89786-04-9].C10H12N4O5S·½H2O
309.30
[428863-55-2].(RB 1-May-2011)DEFINITION
Tazobactam contains NLT 98.0% and NMT 102.0% of C10H12N4O5S, calculated on the anhydrous basis.
IDENTIFICATION
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Mobile phase:
Dissolve 1.32 g of dibasic ammonium phosphate in 750 mL of water. Adjust with 5% v/v phosphoric acid to a pH of 2.5, and dilute with water to 1000 mL. Add 30 mL of acetonitrile, mix, and pass through a filter of 0.2-µm pore size.
System suitability solution:
16 µg/mL of l-phenylalanine, 50 µg/mL of USP Tazobactam RS, and 8 µg/mL of USP Tazobactam Related Compound A RS in Mobile phase. Maintain the System suitability solution at 3
until injection. Prepare fresh daily. If an autosampler is used, replace the plastic tubing connected to the injection needle with a stainless steel assembly, and maintain at 3. If a chilled autosampler is not used, then this solution should be injected immediately after preparation.
until injection. Prepare fresh daily. If an autosampler is used, replace the plastic tubing connected to the injection needle with a stainless steel assembly, and maintain at 3. If a chilled autosampler is not used, then this solution should be injected immediately after preparation.
Standard solution:
0.5 mg/mL of USP Tazobactam RS in Mobile phase. Cool, and maintain the Standard solution at 3 until injection. If an autosampler is used, replace the plastic tubing connected to the injection needle with a stainless steel assembly, and maintain at 3. If a chilled autosampler is not used, then this solution should be injected immediately after preparation.
until injection. If an autosampler is used, replace the plastic tubing connected to the injection needle with a stainless steel assembly, and maintain at 3. If a chilled autosampler is not used, then this solution should be injected immediately after preparation.
Sample solution:
0.5 mg/mL of Tazobactam in Mobile phase. Cool, and maintain the Sample solution at 3 until injection. If an autosampler is used, replace the plastic tubing connected to the injection needle with a stainless steel assembly, and maintain at 3. If a chilled autosampler is not used, then this solution should be injected immediately after preparation.
until injection. If an autosampler is used, replace the plastic tubing connected to the injection needle with a stainless steel assembly, and maintain at 3. If a chilled autosampler is not used, then this solution should be injected immediately after preparation.
Chromatographic system
Mode:
LC
Detector:
UV 210 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Flow rate:
1.5 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
[Note—See Table 1 for the relative retention times. ]
Suitability requirements
Resolution:
NLT 6.0 between tazobactam and l-phenylalanine, System suitability solution
Tailing factor:
NMT 1.8, Standard solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of tazobactam (C10H12N4O5S) in the portion of Tazobactam taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Tazobactam RS in the Standard solution (mg/mL) |
| CU | = | = concentration of the Sample solution (mg/mL) |
Acceptance criteria:
98.0%–102.0% on the anhydrous basis
IMPURITIES
• Residue on Ignition 281:
NMT 0.1%
281:
NMT 0.1%
• Heavy Metals, Method II 231:
NMT 20 ppm
231:
NMT 20 ppm
• Organic Impurities
Mobile phase, System suitability solution, Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Blank:
Mobile phase. Cool, and maintain the Blank at 3 until injection. If an autosampler is used, replace the plastic tubing connected to the injection needle with a stainless steel assembly, and maintain at 3. If a chilled autosampler is not used, then this solution should be injected immediately after preparation.
until injection. If an autosampler is used, replace the plastic tubing connected to the injection needle with a stainless steel assembly, and maintain at 3. If a chilled autosampler is not used, then this solution should be injected immediately after preparation.
Sample solution:
Prepare as directed in the Assay. Cool, and maintain the Sample solution at 3 until injection. If an autosampler is used, replace the plastic tubing connected to the injection needle with a stainless steel assembly, and maintain at 3. If a chilled autosampler is not used, then this solution should be injected immediately after preparation.
until injection. If an autosampler is used, replace the plastic tubing connected to the injection needle with a stainless steel assembly, and maintain at 3. If a chilled autosampler is not used, then this solution should be injected immediately after preparation.
Analysis
Samples:
Blank and Sample solution
Ignore any peaks of the Sample solution that correspond to any peaks of the Blank.
Calculate the percentage of each impurity in the portion of Tazobactam taken:
Result = (rU/rT) × 100
| rU | = | = peak response for each impurity in the Sample solution |
| rT | = | = sum of all the peak responses in the Sample solution |
Acceptance criteria:
See Table 1.
Table 1
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|---|---|---|
| Tazobactam related compound A | 0.29 | 1.0 |
| l-Phenylalanine | 0.71 | — |
| Tazobactam | 1.0 | — |
| Any other individual impurity |
— | 0.1 |
| Total impuritiesa | — | 0.3 |
|
a
Total of all impurities other than tazobactam related compound A.
|
||
SPECIFIC TESTS
• Bacterial Endotoxins Test 85:
The level of bacterial endotoxins is such that the requirements of the relevant dosage form monograph(s) in which Tazobactam is used can be met.
85:
The level of bacterial endotoxins is such that the requirements of the relevant dosage form monograph(s) in which Tazobactam is used can be met.
• Optical Rotation, Specific Rotation 781S
781S
Sample solution:
10 mg/mL, in dimethylformamide
Acceptance criteria:
+160 to +167 (t = 20)
to +167 (t = 20)
• Microbial Enumeration Tests 61 and Tests for Specified Microorganisms 62:
The total aerobic microbial count does not exceed 103 cfu/g, and the total combined molds and yeasts count does not exceed 102 cfu/g.
61 and Tests for Specified Microorganisms 62:
The total aerobic microbial count does not exceed 103 cfu/g, and the total combined molds and yeasts count does not exceed 102 cfu/g.
Change to read:
• Water Determination, Method I 921:
NMT 0.6% for the anhydrous form; 2.2–3.8% for the hemihydrate form(RB 1-May-2011)
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers. Store at controlled room temperature.
Add the following:
• Labeling:
Where it is the hemihydrate form, the label so indicates.(RB 1-May-2011)
• USP Reference Standards 11
11
USP Endotoxin RS
USP Tazobactam RS 
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USP Tazobactam Related Compound A RS
(2S,3S)-2-Amino-3-methyl-3-sulfino-4-(1H-1,2,3-triazol-1-yl)butyric acid.
C7H12N4O4S 248.26
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(2S,3S)-2-Amino-3-methyl-3-sulfino-4-(1H-1,2,3-triazol-1-yl)butyric acid.
C7H12N4O4S 248.26
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ahalya Wise, M.S.
Senior Scientific Liaison 1-301-816-8161 |
(SM12010) Monographs - Small Molecules 1 |
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 61 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 62 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4755
Pharmacopeial Forum: Volume No. 34(2) Page 302