Famotidine Injection

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

Famotidine Injection is a sterile, concentrated solution of Famotidine. It contains NLT 90.0% and NMT 110.0% of the labeled amount of famotidine (C₈H₁₅N₇O₂S₃). It may contain suitable preservatives.

2 IDENTIFICATION

A. The retention time of the famotidine peak from the Sample solution corresponds to that from the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Buffer: 13.8 g/L of monobasic sodium phosphate

Mobile phase: Methanol, water, and Buffer (5:32:3). 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.

3.2 Standard solution

If benzyl alcohol is present: 0.1 mg/mL of USP Famotidine RS and 0.09 mg/mL of USP Benzyl Alcohol RS in Diluent

If benzyl alcohol is not present: 0.1 mg/mL of USP Famotidine RS in Diluent

Sample solution: Transfer a volume of Injection, equivalent to 20 mg of famotidine based on the label claim, to a 200-mL volumetric flask, and dilute with Diluent to volume.

3.3 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 25-cm; 5-μm packing L3

Flow rate: 1 mL/min

Injection size: 30 μL

3.4 System suitability

Sample: Standard solution

3.5 Suitability requirements

Relative standard deviation: NMT 2.0% for the famotidine peak

3.6 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of famotidine (C₈H₁₅N₇O₂S₃) in the portion of Injection taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response of famotidine from the Sample solution

r_S = peak response of famotidine from the Standard solution

C_S = concentration of USP Famotidine RS in the Standard solution (mg/mL)

C_U = nominal concentration of famotidine in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 OTHER COMPONENTS

Content of Benzyl Alcohol (if present)

Buffer, Mobile phase, Diluent, Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability stock solution: Proceed as directed in the Organic Impurities test.

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, and dilute with Diluent to volume.

System suitability

Samples: Standard solution and System suitability solution

[Note-See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.3 between adjacent peaks of benzyl alcohol and famotidine propionic acid; the benzyl alcohol peak is resolved from the solvent front, System suitability solution

Relative standard deviation: Less than 2.0% for each peak, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of benzyl alcohol in the portion of Injection taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak area of benzyl alcohol from the Sample solution

r_S = peak area of benzyl alcohol from the Standard solution

C_S = concentration of USP Benzyl Alcohol RS in the Standard solution (mg/mL)

C_U = nominal concentration of benzyl alcohol in the Sample solution (mg/mL)

Acceptance criteria: The content of benzyl alcohol meets the requirements under Injections and Implanted Drug Products 〈1〉, Specific Tests, Vehicles and added substances.

5 IMPURITIES

5.1 Organic Impurities

Buffer, Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability stock solution: Transfer 10 mg of USP Famotidine RS to a 50-mL volumetric flask. Add 1 mL of 0.1 N hydrochloric acid.

Heat at 80° for 30 min. Allow to cool, add 2 mL of 0.1 N sodium hydroxide, and heat at 80° for an additional 30 min. Allow to cool, and neutralize by adding 1 mL of 0.1 N hydrochloric acid. Dilute with Diluent to volume (Solution A). Transfer 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, and dilute with Diluent to volume.

5.2 System suitability solution

If benzyl alcohol is present: Transfer 25 mL of System suitability stock solution to a 50-mL volumetric flask. Add 1 drop (approximately 20mg) of USP Benzyl Alcohol RS, and dilute with Diluent to volume.

If benzyl alcohol is not present: Transfer 25 mL of System suitability stock solution to a 50-mL volumetric flask, and dilute with Diluent to volume.

5.3 System suitability

Sample: System suitability solution

[Note-See Table 1 for the relative retention times.]

5.4 Suitability requirements

Resolution: NLT 1.3 between adjacent peaks of famotidine propionic acid, famotidine sulfamoyl propanamide, famotidine, and famotidine propanamide for each pair of peaks

5.5 Analysis

Sample: Sample solution

Calculate the percentage of the total of famotidine propionic acid, famotidine sulfamoyl propanamide, and famotidine propanamide in the portion of Injection taken:

Result = (r_U /r_T ) × 100

r_U = sum of the peak areas for famotidine propionic acid, famotidine sulfamoyl propanamide, and famotidine propanamide from the Sample solution

r_T = sum of the peak areas for famotidine, famotidine propionic acid, famotidine sulfamoyl propanamide, and famotidine propanamide from the Sample solution

5.6 Acceptance criteria

Total impurities: NMT 5.0%

Table 1

^a 3-[[2-(Diaminomethyleneamino)thiazol-4-yl]methylthio]propanoic acid.

^b 3-[[2-(Diaminomethyleneamino)thiazol-4-yl]methylthio]-N-sulfamoylpropanamide.

^c 3-[[2-(Diaminomethyleneamino)thiazol-4-yl]methylthio] propanamide.

6 SPECIFIC TESTS

Sterility Tests 〈71〉: Meets the requirements

pH 〈791〉: 5.0–5.6

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections

Bacterial Endotoxins Test 〈85〉: NMT 16.67 USP Endotoxin Units/mg of famotidine

Other Requirements: It meets the requirements under Container Content for Injections 〈697〉.

7 ADDITIONAL REQUIREMENTS

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 under Labeling 〈7〉, Labels and Labeling for Injectable Products. 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.

USP Reference Standards 〈11〉

USP Benzyl Alcohol RS

USP Famotidine RS