Famotidine Injection
» Famotidine Injection is a sterile, concentrated solution of Famotidine. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of famotidine (C8H15N7O2S3). It may contain suitable preservatives.
Packaging and storage—
Preserve in single-dose or multiple-dose containers, preferably of Type I glass. Store in a refrigerator.
Labeling—
It meets the requirements for Labeling under Injections 
1
. Label it to indicate that the Injection is to be diluted with a suitable parenteral vehicle prior to administration. Label it to indicate the name and the quantity of any added preservative.
1. Label it to indicate that the Injection is to be diluted with a suitable parenteral vehicle prior to administration. Label it to indicate the name and the quantity of any added preservative.
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Identification—
The retention time of the famotidine peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Bacterial endotoxins 85—
It contains not more than 16.67 USP Endotoxin Units per mg of famotidine.
85—
It contains not more than 16.67 USP Endotoxin Units per mg of famotidine.
Sterility 71:
meets the requirements.
71:
meets the requirements.
pH 791:
between 5.0 and 5.6.
791:
between 5.0 and 5.6.
Particulate matter 788:
meets the requirements for small-volume injections.
788:
meets the requirements for small-volume injections.
Related compounds—
Buffer solution, Mobile phase, and Diluent—
Proceed as directed in the Assay.
Test solution—
Use the Assay preparation prepared as directed in the Assay.
System suitability stock solution—
Proceed as directed in the test for Content of benzyl alcohol.
System suitability solution—
if benzyl alcohol is present—
Proceed as directed in the test for Content of benzyl alcohol.
if benzyl alcohol is not present—
Transfer 25 mL of System suitability stock solution to a 50-mL volumetric flask, dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621)—
Prepare as directed in the Assay. Chromatograph the System suitability solution, identify the famotidine peak and other peaks based on the relative retention times listed in Table 1, and record the peak responses as directed for Procedure: the resolution, R, between adjacent peaks of impurity B, impurity C, famotidine, and impurity D is not less than 1.3 for each pair of peaks.
621)—
Prepare as directed in the Assay. Chromatograph the System suitability solution, identify the famotidine peak and other peaks based on the relative retention times listed in Table 1, and record the peak responses as directed for Procedure: the resolution, R, between adjacent peaks of impurity B, impurity C, famotidine, and impurity D is not less than 1.3 for each pair of peaks.
Table 1
| Name | Approximate Relative Retention Time |
|---|---|
| Benzyl alcohol (if present) | 0.4 |
| Impurity B1 | 0.7 |
| Impurity C2 | 0.8 |
| Famotidine | 1.0 |
| Impurity D3 | 1.3 |
|
1
3-[2-(Diaminomethyleneamino)-1,3-thiazol-4-ylmethylthio]propanoic acid
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2
3-[2-(Diaminomethyleneamino)-1,3-thiazol-4-ylmethylthio]-N-sulfamoylpropanamide
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3
3-[2-(Diaminomethyleneamino)-1,3-thiazol-4-ylmethylthio]propanamide
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Procedure—
Inject about 30 µL of the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of the total of impurities B, C, and D in the portion of the Injection taken by the formula:
100(rU / rT)
in which rU is the sum of the areas of peaks for impurities B, C, and D obtained from the Test solution; and rT is the sum of the peak areas for famotidine, impurity B, impurity C, and impurity D obtained from the Test solution: not more than 5.0% of total impurities is found.
Content of benzyl alcohol (if present)—
Buffer solution, Mobile phase, and Diluent—
Proceed as directed in the Assay.
Test solution—
Use the Assay preparation prepared as directed in the Assay.
System suitability stock solution—
Transfer approximately 10 mg of USP Famotidine RS to a 50-mL volumetric flask, and add 1 mL of 0.1 N hydrochloric acid. Heat at 80
for 30 minutes. Allow to cool, add 2 mL of 0.1 N sodium hydroxide, and heat at 80 for an additional 30 minutes. Allow to cool, and neutralize by adding 1 mL of 0.1 N hydrochloric acid. Dilute with Diluent to volume, and mix (Solution A). Transfer about 5 mg of USP Famotidine RS to a separate 50-mL volumetric flask, add 8 mL of methanol, and sonicate to dissolve. Add 10 mL of Solution A, dilute with Diluent to volume, and mix.
for 30 minutes. Allow to cool, add 2 mL of 0.1 N sodium hydroxide, and heat at 80 for an additional 30 minutes. Allow to cool, and neutralize by adding 1 mL of 0.1 N hydrochloric acid. Dilute with Diluent to volume, and mix (Solution A). Transfer about 5 mg of USP Famotidine RS to a separate 50-mL volumetric flask, add 8 mL of methanol, and sonicate to dissolve. Add 10 mL of Solution A, dilute with Diluent to volume, and mix.
System suitability solution—
Transfer 25 mL of System suitability stock solution to a 50-mL volumetric flask. Add 1 drop (approximately 20 mg) of USP Benzyl Alcohol RS, dilute with Diluent to volume, and mix.
Standard solution—
Dissolve accurately weighed quantities of USP Famotidine RS and USP Benzyl Alcohol RS in Diluent to obtain a solution having known concentrations of about 0.1 mg of famotidine per mL and about 0.09 mg of benzyl alcohol per mL.
Chromatographic system (see Chromatography 621)—
Prepare as directed in the Assay. Chromatograph the System suitability solution, identify the components based on their relative retention times listed in Table 1, and record the peak responses as directed for Procedure: the benzyl alcohol peak is resolved from the solvent front, and the resolution, R, between adjacent peaks of benzyl alcohol and famotidine impurity B is not less than 1.3. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is less than 2.0% for each peak.
621)—
Prepare as directed in the Assay. Chromatograph the System suitability solution, identify the components based on their relative retention times listed in Table 1, and record the peak responses as directed for Procedure: the benzyl alcohol peak is resolved from the solvent front, and the resolution, R, between adjacent peaks of benzyl alcohol and famotidine impurity B is not less than 1.3. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is less than 2.0% for each peak.
Procedure—
Separately inject equal volumes (about 30 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of benzyl alcohol in each mL of the Injection by the formula:
1.
D(C /V)(rU / rS)
in which D is the volume, in mL, of the Test solution; C is the concentration, in mg per mL, of benzyl alcohol in the Standard solution; V is the volume, in mL, of the Injection taken to prepare the Test solution; and rU and rS are the peak areas for benzyl alcohol obtained from the Test solution and the Standard solution, respectively: the content of benzyl alcohol meeets the requirements for Added Substances under Injections 1.
Other requirements—
It meets the requirements for Volume in Container under Injections 1.
1.
Assay—
Buffer solution—
Dissolve 13.8 g of monobasic sodium phosphate in water, and dilute with water to 1 L.
Mobile phase—
Prepare a mixture of water, methanol, and Buffer solution (32:5:3), and adjust with 1 N sodium hydroxide to a pH of 5.3.
Diluent—
Dissolve 1.36 g of monobasic potassium phosphate in 800 mL of water, adjust with 1 N sodium hydroxide to a pH of 7.0, and dilute with water to 1 L.
Standard preparation—
if benzyl alcohol is present—
Dissolve accurately weighed quantities of USP Famotidine RS and USP Benzyl Alcohol RS in Diluent to obtain a solution having known concentrations of about 0.1 mg of famotidine per mL and about 0.09 mg of benzyl alcohol per mL.
if benzyl alcohol is not present—
Dissolve an accurately weighed quantity of USP Famotidine RS in Diluent to obtain a solution having a known concentration of about 0.1 mg of famotidine per mL.
Assay preparation—
Transfer an accurately measured volume of Injection, equivalent to about 20 mg of famotidine based on the label claim, to a 200-mL volumetric flask, and dilute with Diluent to volume.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L3. The flow rate is about 1.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections for the famotidine peak is less than 2.0%.
621)—
The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L3. The flow rate is about 1.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections for the famotidine peak is less than 2.0%.
Procedure—
Separately inject equal volumes (about 30 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of famotidine (C8H15N7O2S3) in each mL of the Injection by the formula:
D(C/V)(rU / rS)
in which D is the volume, in mL, of the Assay preparation; C is the concentration, in mg per mL, of famotidine in the Standard preparation; V is the volume, in mL, of Injection taken to prepare the Assay preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Elena Gonikberg, Ph.D.
Principal Scientific Liaison 1-301-816-8251 |
(SM32010) Monographs - Small Molecules 3 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
|
| 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 |
USP35–NF30 Page 3150
Pharmacopeial Forum: Volume No. 37(3)