A:Infrared Absorption á197Kñ.

B: Thin-Layer Chromatographic Identification Test á201ñ—

Test solution: 125mg per mL,in methanol.

Standard solution— Transfer 10.0µLeach of methanol,isopropyl alcohol,and acetone to a 100-mLvolumetric flask,dilute with N,N-dimethylacetamide to volume,and mix.Dilute 10.0mLof this solution with 10.0mLof N,N-dimethylacetamide to obtain a solution containing about 0.04mg of each per mL.

Test solution— Transfer about 100mg of Sotalol Hydrochloride,accurately weighed,to a 25-mLflask,dissolve in 10.0mLof N,N-dimethylacetamide,and mix.[NOTE—Do not dilute to volume.]

Chromatographic system(see Chromatography á621ñ)— The gas chromatograph is equipped with a flame-ionization detector and a 2.0-mm ×1.8-m glass column containing 5%phase G16on 60-to 80-mesh support S12.The injection port temperature is maintained at 200,and the detector temperature is maintained at 300.The column temperature is maintained at 70for 5minutes,then increased at a rate of 30per minute to 180,and maintained at 180for 3minutes.Helium is used as the carrier gas,flowing at a rate of about 30mLper minute.Chromatograph the Standard solution,and record the peak areas as directed for Procedure:the relative retention times are 1.0,1.4,and 2.7for methanol,acetone,and isopropyl alcohol,respectively;the resolution,R,between methanol and acetone and between acetone and isopropyl alcohol is not less than 2.0;and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 1µL)of the Test solutionand the Standard solutioninto the chromatograph,record the chromatograms,and measure the methanol,isopropyl alcohol,and acetone peak areas.Calculate the percentages of methanol,isopropyl alcohol,and acetone in the portion of Sotalol Hydrochloride taken by the formula: in which Cis the concentration,in mg per mL,of the appropriate analyte in the Standard solution;Wis the quantity,in mg,of Sotalol Hydrochloride taken to prepare the Test solution;and rUand rSare the peak areas of the corresponding analyte obtained from the Test solutionand the Standard solution,respectively:not more than 0.3%each of methanol,isopropyl alcohol,and acetone is found;and not more than 0.5%total of methanol,isopropyl alcohol,and acetone is found.

Mobile phase— Proceed as directed in the Assay.

Standard solution— Dissolve accurately weighed quantities of USP Sotalol Hydrochloride RS,USP Sotalol Related Compound A RS,USP Sotalol Related Compound B RS,and USP Sotalol Related Compound C RSin Mobile phase,and dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having known concentrations of about 6µg of each per mL.

Test solution— Transfer about 200mg of Sotalol Hydrochloride,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with Mobile phaseto volume,and mix.

Chromatographic system— Prepare as directed in the Assay.Chromatograph the Standard solution,and record the peak heights as directed for Procedure:the relative retention times are about 0.65for sotalol hydrochloride related compound B,1.0for sotalol hydrochloride,1.2for sotalol hydrochloride related compound A,and 1.4for sotalol hydrochloride related compound C;the resolution,R,between sotalol hydrochloride related compound Aand sotalol hydrochloride is not less than 2.0;and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 25µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the heights for the major peaks.Calculate the percentage of each sotalol hydrochloride related compound in the portion of Sotalol Hydrochloride taken by the formula: in which Cis the concentration,in µg per mL,of the appropriate USP Related Compound Reference Standard in the Standard solution;Wis the weight,in mg,of Sotalol Hydrochloride taken to prepare the Test solution;and riand rSare the peak heights for the corresponding related compound obtained from the Test solutionand the Standard solution,respectively.Calculate the percentage of other impurities in the portion of Sotalol Hydrochloride taken by the formula: in which Cis the concentration,in mg per mL,of USP Sotalol Hydrochloride RSin the Standard solution;Wis the weight,in mg,of Sotalol Hydrochloride taken to prepare the Test solution;rsiis the sum of the peak heights for all impurities,other than the related compounds,obtained from the Test solution;and rSis the peak height of sotalol obtained from the Standard solution.Not more than 0.3%each of sotalol hydrochloride related compound Aand sotalol hydrochloride related compound Bis found;not more than 0.4%of sotalol hydrochloride related compound Cis found;not more than 0.3%of other impurities is found;and not more than 0.5%of total impurities is found.

Diluent— Prepare a mixture of water and acetonitrile (4:1).

Mobile phase— Transfer about 1.08g of sodium 1-octanesulfonate to a 1000-mLvolumetric flask.Dissolve in 10mLof glacial acetic acid and about 70mLof water.Add 720mLof water,dilute with acetonitrile to volume,and mix.Filter,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Internal standard solution— Transfer about 450mg of caffeine to a 100-mLvolumetric flask.Dissolve in and dilute with Diluentto volume,and mix.

Standard preparation— Transfer about 50mg of USP Sotalol Hydrochloride RS,accurately weighed,to a 25-mLvolumetric flask.Dissolve in and dilute with Diluentto volume,and mix.Transfer 10.0mLof this solution and 5.0mLof Internal standard solutionto a 100-mLvolumetric flask.Dilute with Diluentto volume,and mix.

Assay preparation— Transfer about 100mg of Sotalol Hydrochloride,accurately weighed,to a 50-mLvolumetric flask.Dissolve in and dilute with Diluentto volume,and mix.Pipet 10.0mLof this solution and 5.0mLof Internal standard solutioninto a 100-mLvolumetric flask.Dilute with Diluentto volume,and mix.

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 238-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1.5mLper minute.Chromatograph the Standard preparation,and record the peak areas as directed for Procedure:the relative retention times are about 1.0for sotalol and 0.39for caffeine;the resolution,R,between caffeine and sotalol is not less than 8.5;and the relative standard deviation for replicate injections,determined from peak area ratios,is not more than 2.0%.

Procedure— Separately inject equal volumes (about 25µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the quantity,in mg,of C12H20N2O3S·HCl in the portion of Sotalol Hydrochloride taken by the formula: in which Cis the concentration,in mg per mL,of USP Sotalol Hydrochloride RSin the Standard preparation;and RUand RSare the peak area ratios of sotalol to caffeine obtained from the Assay preparationand the Standard preparation,respectively.