Ampicillin Sodium
C16H18N3NaO4S 371.39
4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, [6-(aminophenylacetyl)amino]-3,3-dimethyl-7-oxo-, monosodium salt, [2S-[2
,5,6
(S*)]]-;
Monosodium D-(
)-6-(2-amino-2-phenylacetamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
[69-52-3].
(am'' pi sil' in soe' dee um).
C16H18N3NaO4S 371.39
4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, [6-(aminophenylacetyl)amino]-3,3-dimethyl-7-oxo-, monosodium salt, [2S-[2
,5,6(S*)]]-;
Monosodium D-(
)-6-(2-amino-2-phenylacetamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
[69-52-3].DEFINITION
Ampicillin Sodium has a potency equivalent to NLT 845 µg and NMT 988 µg of ampicillin (C16H19N3O4S) per mg, calculated on the anhydrous basis.
IDENTIFICATION
ASSAY
• Procedure
Diluent:
Water, 1 M monobasic potassium phosphate, and 1 N acetic acid (989:10:1)
Mobile phase:
Acetonitrile, water, 1 M monobasic potassium phosphate, and 1 N acetic acid (80:909:10:1)
Standard solution:
1 mg/mL of USP Ampicillin RS in Diluent using shaking and sonication, if necessary, to dissolve. Use this solution promptly after preparation.
System suitability solution:
0.12 mg/mL of caffeine in Standard solution
Sample solution:
[Note—Ampicillin Sodium is hygroscopic. Minimize exposure to the atmosphere, and weigh promptly. ] Equivalent to 1 mg/mL of anhydrous ampicillin in Diluent. [Note—Use this solution promptly after preparation. ]
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column
Pre-column:
4-mm × 5-cm; 5- to 10-µm packing L1
Analytical column:
4-mm × 30-cm; 5- to 10-µm packing L1
Flow rate:
2 mL/min
Injection size:
20 µL
System suitability
Samples:
Standard solution and System suitability solution
[Note—The relative retention times for ampicillin and caffeine are 0.5 and 1.0, respectively, System suitability solution. ]
Suitability requirements
Resolution:
NLT 2.0 between the caffeine and the ampicillin peaks, System suitability solution
Tailing factor:
NMT 1.4, Standard solution
Capacity factor:
NMT 2.5, Standard solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the quantity, in µg, of C16H19N3O4S in each mg of Ampicillin Sodium taken:
Result = (rU/rS) × (CS/CU) × P
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Ampicillin RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of Ampicillin Sodium in the Sample solution (mg/mL) |
| P | = | = potency of USP Ampicillin RS (µg/mg) |
Acceptance criteria:
845–988 µg/mg on the anhydrous basis
IMPURITIES
Organic Impurities
• Procedure 1: Limit of Methylene Chloride
Internal standard solution:
2.1 mg/mL of dioxane in dimethyl sulfoxide
Standard solution:
0.33 mg/mL of methylene chloride in Internal standard solution
Sample solution:
166.7 mg/mL of Ampicillin Sodium in Internal standard solution
Chromatographic system
Mode:
GC
Detector:
Flame ionization
Column:
1.8-m × 4-mm glass column packed with a 10% phase G39 on unsilanized support S1A
Temperature
Column:
65
Injector:
100
Detector block:
260
Carrier gas:
Nitrogen
Flow rate:
60 mL/min
Injection size:
1 µL
System suitability
Sample:
Standard solution
[Note—The relative retention times for methylene chloride and dioxane are 0.5 and 1.0, respectively. ]
Suitability requirements
Resolution:
NLT 4 between methylene chloride and dioxane
Relative standard deviation:
NMT 5%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of methylene chloride in the portion of Ampicillin Sodium taken:
Result = (RU/RS) × (CS/CU) × 100
| RU | = | = peak response ratio of methylene chloride to dioxane from the Sample solution |
| RS | = | = peak response ratio of methylene chloride to dioxane from the Standard solution |
| CS | = | = concentration of methylene chloride in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of Ampicillin Sodium in the Sample solution (mg/mL) |
Acceptance criteria:
NMT 0.2%.
• Procedure 2: Dimethylaniline 
223
:
Meets the requirement
223:
Meets the requirement
SPECIFIC TESTS
• Crystallinity 695:
Meets the requirements. [Note—Ampicillin Sodium in the freeze-dried form is exempt from this requirement. ]
695:
Meets the requirements. [Note—Ampicillin Sodium in the freeze-dried form is exempt from this requirement. ]
• Water Detemination, Method I 921:
NMT 2.0%
921:
NMT 2.0%
• Sterility Tests 71:
Where the label states that Ampicillin Sodium is sterile, it meets the requirements.
71:
Where the label states that Ampicillin Sodium is sterile, it meets the requirements.
• Bacterial Endotoxins Test 85:
Where the label states that Ampicillin Sodium is sterile or the label states that Ampicillin Sodium must be subjected to further processing during the processing of injectable dosage forms, it contains NMT 0.15 USP Endotoxin Unit/mg of ampicillin.
85:
Where the label states that Ampicillin Sodium is sterile or the label states that Ampicillin Sodium must be subjected to further processing during the processing of injectable dosage forms, it contains NMT 0.15 USP Endotoxin Unit/mg of ampicillin.
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.
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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 |
| 71 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 85 |
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 2213
Pharmacopeial Forum: Volume No. 35(1) Page 65