Famotidine for Oral Suspension

» Famotidine for Oral Suspension contains the equivalent of not less than 90.0 percent and not more than 110.0 percent of the labeled amount of famotidine (C8H15N7O2S3) when constituted as directed. It contains one or more suitable buffers, colors, diluents, flavors, and preservatives.

Packaging and storage— Preserve in tight containers, protected from light. Store at 25

, excursions permitted between 15

and 30

USP Reference standards

—

USP Famotidine RS

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.

Microbial enumeration tests

and Tests for specified microorganisms

— The total aerobic microbial count is not more than 100 cfu per g. The total combined molds and yeasts count is not more than 100 cfu per g. It meets the requirements of the tests for the absence of Salmonella species and Escherichia coli.

791

: between 6.5 and 7.5, in the suspension constituted as directed in the labeling.

Uniformity of dosage units

905

: meets the requirements for Content Uniformity. For the product in multi-dose containers, the unit is a 5-mL aliquot of the suspension, constituted as directed in the labeling.

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
0–15	100	0	isocratic
15–42	100®52	0®48	linear gradient
42–43	52®100	48®0	linear gradient
43–45	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 (C8H15N7O2S3) 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.

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
61	Radhakrishna S Tirumalai, Ph.D. Principal Scientific Liaison 1-301-816-8339	(GCM2010) General Chapters - Microbiology
62	Radhakrishna S Tirumalai, Ph.D. Principal Scientific Liaison 1-301-816-8339	(GCM2010) General Chapters - Microbiology

USP35–NF30 Page 3152

Pharmacopeial Forum: Volume No. 37(3)