Packaging and storage
Preserve in tight containers, protected from light. Store at 25
, excursions permitted between 15
and 30
.
Related compounds
Buffer solution, Solution A, Solution B, and Diluent
Prepare as directed in the Assay.
Standard solution
Use the Standard preparation, prepared as directed in the Assay.
System suitability stock solution
Weigh approximately 16 mg of Famotidine into a 50-mL volumetric flask, dissolve in 1.0 mL of 1 N hydrochloric acid, heat at 80
for 30 minutes, and cool to room temperature. Add 2.0 mL of 1 N sodium hydroxide, heat at 80
for 30 minutes, and cool to room temperature. Add 1.0 mL of 1 N hydrochloric acid to neutralize, and dilute with
Diluent to volume.
System suitability solution
Weigh approximately 16 mg of Famotidine into a 50-mL volumetric flask, add 10 mL of
Diluent, and sonicate to dissolve. Add 5 drops of hydrogen peroxide solution, heat at 80
for 15 minutes, and cool to room temperature. Add 20 mL of
System suitability stock solution, and dilute with
Diluent to volume.
Test solution
Use the Assay preparation, prepared as directed in the Assay.
Chromatographic system (see Chromatography 621)
Proceed as directed in the
Assay, with the following addition. 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 famotidine and impurity D is greater than 1.5.
Table 1
Name |
Approximate Relative Retention Time |
Impurity A1 |
0.3 |
Impurity B2 |
0.5 |
Impurity C3 |
0.7 |
Impurity D4 |
1.2 |
1
3-[2-(diaminomethyleneamino)-1,3-thiazol-4-ylmethylsulfinyl]-N-sulfamoyl-propanamidine
|
2
3-[2-(diaminomethyleneamino)-1,3-thiazol-4-ylmethylthio]-propanoic acid
|
3
3-[2-(diaminomethyleneamino)-1,3-thiazol-4-ylmethylthio]-N-sulfamoyl-propanamide
|
4
3-[2-(diaminomethyleneamino)-1,3-thiazol-4-ylmethylthio]- propanamide
|
Procedure
Separately inject equal volumes (about 20 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 percentage, of the total of impurities C and D in the portion of Famotidine for Oral Suspension taken by the formula:
625CS (ru / rS),
in which
CS is the concentration, in mg per mL, of
USP Famotidine RS in the
Standard solution; ru is the sum of the peak areas for impurities C and D obtained from the
Test solution; and
rS is the famotidine peak area obtained from the
Standard solution: the total of impurities C and D is less than 2%.
Assay
Buffer solution
Dissolve 13.6 g of sodium acetate trihydrate in 900 mL of water, adjust with glacial acetic acid to a pH of 6.0 ± 0.1, and dilute with water to 1 L.
Solution A
Prepare a mixture of Buffer solution and acetonitrile (93:7).
Solution B
Use acetonitrile.
Diluent
Dissolve 13.6 g of monobasic sodium phosphate in 900 mL of water, adjust with 1 M sodium hydroxide to a pH of 7.0 ± 0.1, and dilute with water to 1 L. Mix 930 mL of this solution with 70 mL of acetonitrile.
Standard preparation
Dissolve an accurately weighed quantity of
USP Famotidine RS in
Diluent to obtain a solution having a known concentration of about 0.16 mg per mL.
Assay preparation
Transfer to a 100-mL volumetric flask an accurately measured portion of Famotidine for Oral Suspension, freshly mixed and free from air bubbles and constituted as directed in the labeling, equivalent to about 40 mg of famotidine, based on the labeled amount per mL of Famotidine for Oral Suspension. Add 10 mL of methanol, sonicate for 5 minutes, add 70 mL of Diluent, sonicate for an additional 5 minutes, and dilute with Diluent to volume. Dilute 10.0 mL of this solution with Diluent to 25.0 mL, and filter.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 268-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The column temperature is maintained at 35
. The flow rate is about 1.5 mL per minute. The chromatograph is programmed as follows.
Time (minutes) |
Solution A
(%) |
Solution B
(%) |
Elution |
015 |
100 |
0 |
isocratic |
1542 |
100®52 |
0®48 |
linear gradient |
4243 |
52®100 |
48®0 |
linear gradient |
4345 |
100 |
0 |
isocratic |
Chromatograph the
Standard preparation, and record the peak responses as directed for
Procedure: the tailing factor is not more than 2; the column efficiency is greater than 2000 theoretical plates; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure
Separately inject equal volumes (about 20 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 (C
8H
15N
7O
2S
3) in the portion of Famotidine for Oral Suspension taken by the formula:
CD(rU / rS),
in which
C is the concentration, in mg per mL, of
USP Famotidine RS in the
Standard preparation; D is the dilution factor, in mL, for famotidine in the
Assay preparation; and
rU and
rS are the peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.