Protamine Sulfate for Injection
DEFINITION
Protamine Sulfate for Injection is a sterile mixture of Protamine Sulfate with one or more suitable, dry diluents. Each mg of Protamine Sulfate, used in the manufacture of the Protamine Sulfate for Injection, neutralizes NLT 100 USP Heparin Units, calculated on the dried basis. It contains NLT 90.0% and NMT 120.0% of the labeled amount of protamine sulfate.
ASSAY
• Procedure
Sample solution:
0.15 mg/mL of protamine sulfate in Water for Injection. Dissolve from the contents of 1 container of Protamine Sulfate for Injection.
Analysis:
[Note—Titrate the Sample solution in duplicate. ] Transfer the same volume of the Sample solution to the analytical cell as used in the Assay for the drug substance. Proceed as directed in the Assay under Protamine Sulfate, using the same concentration of Titrant and the same wavelength as used in the Assay for the drug substance. The concentration of the Sample solution of the drug substance should also be 0.15 mg/mL. Perform the entire Assay in triplicate, and calculate the average of the triplicate determinations. The percentage of the label claim is given as follows:
Result = (v/V) × 100
| v | = | = volume of Titrant added to the Protamine Sulfate for Injection Sample solution (mL) |
| V | = | = volume of Titrant added to the drug substance Sample solution (mL) |
Acceptance criteria:
90.0%–120.0%
PERFORMANCE TESTS
• Uniformity of Dosage Units 
905
:
Meets the requirements
905:
Meets the requirements
SPECIFIC TESTS
• Injections, Constituted Solutions 1:
At the time of use, it meets the requirements.
1:
At the time of use, it meets the requirements.
• Bacterial Endotoxins Test 85:
It contains NMT 7.0 USP Endotoxin Units/mg of protamine sulfate.
85:
It contains NMT 7.0 USP Endotoxin Units/mg of protamine sulfate.
• Sterility Tests 71:
Both it and the accompanying solvent meet the requirements
71:
Both it and the accompanying solvent meet the requirements
• pH and Clarity of Solution:
Dissolve it in the solvent recommended in the labeling: the pH of the solution is 6.5–7.5, and the solution is clear.
• Other Requirements:
Both it and the accompanying solvent meet the requirements for Injections 1, Labeling.
1, Labeling.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve as described under Injections 1, Containers for Sterile Solids. Preserve the accompanying solvent in single-dose or in multiple-dose containers, preferably of Type I glass.
1, Containers for Sterile Solids. Preserve the accompanying solvent in single-dose or in multiple-dose containers, preferably of Type I glass.
• Labeling:
Label it to indicate the approximate neutralization capacity in USP Heparin Units.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Anita Y. Szajek, Ph.D.
Principal Scientific Liaison 1-301-816-8325 |
(BIO12010) Monographs - Biologics and Biotechnology 1 |
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| 71 |
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 4473
Pharmacopeial Forum: Volume No. 36(3) Page 647