Famotidine

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

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

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C₈H₁₅N₇O₂S₃ 337.45

Propanimidamide, N'-(aminosulfonyl)-3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]-;

[1-Amino-3-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl]thio]propylidene]sulfamide;

3-[[2-(Diaminomethyleneamino)thiazol-4-yl]methylthio]-N'-sulfamoylpropanimidamide CAS RN^®: 76824-35-6; UNII: 5QZO15J2Z8.

1 DEFINITION

Famotidine contains NLT 98.5% and NMT 101.0% of famotidine (C₈H₁₅N₇O₂S₃), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy, 1974, 197K, or 197M (CN 1-May-2020)

3 ASSAY

PROCEDURE

Sample: Dissolve 250 mg of Famotidine in 80 mL of glacial acetic acid.

Analysis: Titrate with 0.1 N perchloric acid VS (see Titrimetry (541)), using a suitable anhydrous electrode system. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 16.87 mg of C₈H₁₅N₇O₂S₃.

Acceptance criteria: 98.5%-101.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

Buffer: 1.882 g/L of sodium 1-hexanesulfonate in water, adjusted with acetic acid to a pH of 3.5

Solution A: Acetonitrile, methanol, and Buffer (94:6:900)

Solution B: Acetonitrile

Mobile phase: See Table 1. [NOTE-If necessary, adjust the Mobile phase to achieve a retention time of 19-23 min for the famotidine peak and a maximum of 48 min for the famotidine related compound E peak.]

Table 1

Standard stock solution: 0.5 mg/mL of USP Famotidine RS in Solution A

Standard solution: 0.5 µg/mL of USP Famotidine RS in Solution A

System suitability stock solution: 0.25 mg/mL of USP Famotidine Related Compound D RS in methanol

System suitability solution: Transfer 1 mL of the System suitability stock solution and 0.5 mL of the Standard stock solution into a 100-mL volumetric flask, and dilute with Solution A to volume.

Sample solution: 0.5 mg/mL of Famotidine in Solution A

Identification solution: 0.5 mg/mL of USP Famotidine RS and 1.5 µg/mL of each of USP Famotidine Related Compound B RS, USP Famotidine Related Compound C RS, USP Famotidine Related Compound D RS. USP Famotidine Related Compound E RS, and USP Famotidine Related Compound F RS in Solution A

[NOTE-To address the poor solubility of USP Famotidine Related Compound F RS in Solution A, it may be first dissolved in a minimal amount of 0.1 N sodium hydroxide.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 265 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 50°

Flow rate: See Table 1.

Injection volume: 20 µL

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 3.5 between famotidine and famotidine related compound D

Analysis

Samples: Standard solution, Sample solution, and Identification solution

Chromatograph the Identification solution, and identify the components on the basis of their relative retention times, given in Table 2. Calculate the percentage of each impurity in the portion of Famotidine taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) x 100

r_U = peak response of each impurity 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 = concentration of Famotidine in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a Famotidine propanamide.

^b Famotidine sulfamoyl propanamide.

^c N-Cyano-3-[[2-(diaminomethyleneamino)thiazol-4-yl]methylthio]propanimidamide.

^d Famotidine propionic acid.

^e 3-[[2-(Diaminomethyleneamino)thiazol-4-yl]methylthio]propanimidamide.

^f Famotidine dimer.

^g Famotidine disulfide.

5 SPECIFIC TESTS

LOSS ON DRYING (731).

Analysis: Dry a sample at a pressure not exceeding 5 mm of mercury at 80° for 5 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers, protected from light. Store at room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Famotidine RS

USP Famotidine Related Compound B RS

3,5-Bis[2-[[2-[(diaminomethylene)amino]thiazol-4-yl]methylthio]ethyl]-4H-1,2,4,6-thiatriazine 1,1-dioxide.

C₁₆H₂₃N₁₁O₂S₅ 561.73

USP Famotidine Related Compound C RS

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

C₈H₁₃CIN₆O₃S₃ 374.88

USP Famotidine Related Compound D RS

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

C₈H₁₃N₅OS₂ 259.35

USP Famotidine Related Compound E RS

2,2'-[4,4'-Disulfanediylbis(methylene)bis(thiazole-4,2-diyl)]diguanidine.

C₁₀H₁₄N₈S₄ 374.53

USP Famotidine Related Compound F. RS

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

C₈H₁₂N₄O₂S₂ 260.34