A: Thin-Layer Chromatographic Identification Test 201—

B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.

Medium: pH 4.5, 0.1 M phosphate buffer; prepared by dissolving 13.6 g of monobasic potassium phosphate in 1 L of water; 900 mL.

Apparatus 2: 50 rpm.

Time: 30 minutes.

spectrophotometric method— Determine the amount of C8H15N7O2S3 dissolved from UV absorption at the wavelength of maximum absorbance at about 265 nm, using filtered portions of the solution under test, suitably diluted with Medium if necessary, in comparison with a Standard solution having a known concentration of USP Famotidine RS in the same Medium.

chromatographic method—

Tolerances— Not less than 75% (Q) of the labeled amount of C8H15N7O2S3 is dissolved in 30 minutes.

for tablets labeled as chewable— Proceed as directed for either of the methods specified above, except for the following:

for tablets labeled as film-coated— Proceed as directed for either of the methods specified above, except for the following:

Buffer solution, Mobile phase, Diluent, System suitability solution, and Chromatographic system— Proceed as directed in the Assay.

Standard solution— Use the Standard preparation as prepared in the Assay.

Test solution— Use the Assay preparation as prepared in the Assay.

Procedure— Separately inject equal volumes (about 50 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 percentage of each impurity in the portion of Tablets taken by the formula: in which F is the relative response factor for each impurity peak (see Table 1 for values); C is the concentration, in mg per mL, of USP Famotidine RS in the Standard solution; L is the labeled amount, in mg, of famotidine in each Tablet; N is the number of Tablets taken to prepare the Test solution; D is the dilution factor used to prepare the Test solution; ri is the peak area obtained for each individual impurity in the Test solution; and rS is the peak area for famotidine in the Standard solution. In addition to not exceeding the limits for each impurity in Table 1, not more than 1.5% of total impurities is found.

Buffer solution— Dissolve 13.6 g of sodium acetate trihydrate in 750 mL of water. Add 1 mL of triethylamine, adjust with glacial acetic acid to a pH of 6.0, and dilute with water to 1 L.

Mobile phase— Prepare a mixture of Buffer solution and acetonitrile (93:7), mix, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).

Diluent— Dissolve 6.8 g of monobasic potassium phosphate in 750 mL of water, adjust with 1 M potassium hydroxide to a pH of 6.0, and dilute with water to 1 L.

System suitability stock solution— Transfer 10 mg of famotidine to a 50-mL volumetric flask, add 1 mL of 0.1 N hydrochloric acid, heat at 80 for 30 minutes, and cool to room temperature. Add 2 mL of 0.1 N sodium hydroxide, heat at 80 for 30 minutes, cool to room temperature, and neutralize by adding 1 mL of 0.1 N hydrochloric acid. Dilute with Diluent to volume. Transfer 10 mL of this solution to a separate 50-mL volumetric flask containing 5 mg of famotidine dissolved in 8 mL of methanol. Dilute with Diluent to volume. Transfer 25 mL of this solution to a 50-mL volumetric flask, and dilute with Diluent to volume. [note—This solution is stable for up to 1 month.]

System suitability solution— Transfer approximately 1 to 1.5 mL of the System suitability stock solution to a suitable container, add 1 drop of hydrogen peroxide solution, and mix well. [note—Prepare fresh daily.]

Standard preparation— Transfer about 10 mg of USP Famotidine RS, accurately weighed, into a 100-mL volumetric flask, add 20 mL of methanol, and sonicate for 5 minutes. Dilute with Diluent to volume, and mix.

Assay preparation— Transfer not fewer than 10 Tablets to a 1-L volumetric flask. Add 200 mL of Diluent, and swirl to erode the Tablets. Add 200 mL of methanol, and stir by mechanical means at 300 rpm for 1 hour. Dilute with Diluent to volume, mix, and filter. Quantitatively dilute a portion of the clear filtrate with Diluent to obtain a solution containing about 0.1 mg of famotidine per mL.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 275-nm detector and a 4.6-mm × 15-cm column that contains packing L1. The column temperature is maintained at 40. The flow rate is about 1.4 mL per minute. Chromatograph the System suitability solution, and identify the famotidine peak and the peaks due to impurities listed in Table 1. Record the peak responses as directed for Procedure: the resolution, R, between the impurity C and famotidine peaks is not less than 1.3; the resolution, R, between the famotidine and impurity D peaks is not less than 1.3; and the capacity factor, k¢, for the famotidine peak is not less than 2.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is less than 2.0%.

Procedure— Separately inject equal volumes (about 50 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 Tablet taken by the formula: in which C is the concentration, in mg per mL, of USP Famotidine RS in the Standard preparation; D is the dilution factor used to prepare the Assay preparation; N is the number of Tablets taken to prepare the Assay preparation; and rU and rS are the peak areas obtained from the Assay preparation and the Standard preparation, respectively.