A: Infrared Absorption á197Kñ.

B: Ultraviolet Absorption á197Uñ—

Solution: 14µg per mL.

Medium: 0.1Nsulfuric acid.

Mobile phase— Transfer about 940mg of sodium 1-hexanesulfonate to a 1000-mLvolumetric flask,add 240mLof methanol followed by 0.3mLof phosphoric acid,and dilute with water to volume.Mix,and filter.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Test solution 1— Transfer about 100mg of Cimetidine Hydrochloride,accurately weighed,to a 250-mLvolumetric flask,dissolve in and dilute with Mobile phaseto volume,and mix.

Test solution 2— Transfer 1.0mLof Test solution 1to a 500-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.

Resolution solution— Dissolve about 50mg of Cimetidine Hydrochloride in 10mLof 1Nhydrochloric acid,and heat on a steam bath for about 10minutes (or boil on a hot plate for about 2minutes),and allow to cool.Dilute a suitable volume of this solution with Mobile phaseto obtain a solution having a concentration of about 2µg per mL.[NOTE—Use this solution within 24hours of its preparation.Adjustment of the heating step may be necessary to achieve a satisfactory amide analog peak response for the measurement of the resolution between the cimetidine and the amide analog peaks.]

Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm ×25-cm column that contains packing L1.The flow rate is about 2mLper minute.Chromatograph the Resolution solution,and record the peak responses as directed for Procedure:the resolution,R,between the cimetidine and the amide analog peaks is not less than 4.0.Chromatograph Test solution 2,and record the peak responses as directed for Procedure:the capacity factor,k¢,is not less than 3.0;the column efficiency is not less than 2000theoretical plates;and the relative standard deviation for replicate injections is not more than 7.0%.

Procedure— Separately inject equal volumes (about 50µL)of Test solution 1and Test solution 2into the chromatograph,record the chromatograms,and measure the peak responses.Calculate the percentage of each impurity in the portion of Cimetidine Hydrochloride taken by the formula: in which riis the peak response for an individual impurity observed in the chromatogram obtained from Test solution 1,and rSis the peak response of cimetidine in the chromatogram obtained from Test solution 2:no single impurity is greater than 0.2%,and the sum of all impurities is not more than 1.0%.

Mobile phase— Transfer 200mLof methanol and 0.3mLof phosphoric acid to a 1000-mLvolumetric flask,dilute with water to volume,mix,and filter.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard preparation— Dissolve an accurately weighed quantity of USP Cimetidine Hydrochloride RSin a mixture of water and methanol (80:20)to obtain a solution having a known concentration of about 0.5mg per mL.Transfer 5.0mLof this solution to a 200-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.

Assay preparation— Transfer about 115mg of Cimetidine Hydrochloride,accurately weighed,to a 250-mLvolumetric flask,dissolve in about 50mLof water,add 50mLof methanol,and dilute with water to volume.Transfer 5.0mLof this solution to a 200-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.

Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 220-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the capacity factor,k¢,is not less than 0.6;the column efficiency determined from the analyte peak is not less than 1000theoretical plates;and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 50µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the peak responses.Calculate the quantity,in mg,of C10H16N6S·HCl in the portion of Cimetidine Hydrochloride taken by the formula: in which Cis the concentration,in µg per mL,of USP Cimetidine Hydrochloride RSin the Standard preparation;and rUand rSare the cimetidine peak responses obtained from the Assay preparationand the Standard preparation,respectively.