A: Infrared Absorption 197K.

B: Thin-Layer Chromatographic Identification Test 201—

Test solution: 125 mg per mL, in methanol.

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

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

Chromatographic system (see Chromatography 621)— The gas chromatograph is equipped with a flame-ionization detector and a 2.0-mm × 1.8-m glass column containing 5% phase G16 on 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 70 for 5 minutes, then increased at a rate of 30 per minute to 180, and maintained at 180 for 3 minutes. Helium is used as the carrier gas, flowing at a rate of about 30 mL per minute. Chromatograph the Standard solution, and record the peak areas as directed for Procedure: the relative retention times are 1.0, 1.4, and 2.7 for 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 1 µL) of the Test solution and the Standard solution into 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 C is the concentration, in mg per mL, of the appropriate analyte in the Standard solution; W is the quantity, in mg, of Sotalol Hydrochloride taken to prepare the Test solution; and rU and rS are the peak areas of the corresponding analyte obtained from the Test solution and 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 RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having known concentrations of about 6 µg of each per mL.

Test solution— Transfer about 200 mg of Sotalol Hydrochloride, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Mobile phase to 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 0.65 for sotalol hydrochloride related compound B, 1.0 for sotalol hydrochloride, 1.2 for sotalol hydrochloride related compound A, and 1.4 for sotalol hydrochloride related compound C; the resolution, R, between sotalol hydrochloride related compound A and 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 25 µL) of the Standard solution and the Test solution into 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 C is the concentration, in µg per mL, of the appropriate USP Related Compound Reference Standard in the Standard solution; W is the weight, in mg, of Sotalol Hydrochloride taken to prepare the Test solution; and ri and rS are the peak heights for the corresponding related compound obtained from the Test solution and the Standard solution, respectively. Calculate the percentage of other impurities in the portion of Sotalol Hydrochloride taken by the formula: in which C is the concentration, in µg per mL, of USP Sotalol Hydrochloride RS in the Standard solution; W is the weight, in mg, of Sotalol Hydrochloride taken to prepare the Test solution; rsi is the sum of the peak heights for all impurities, other than the related compounds, obtained from the Test solution; and rS is the peak height of sotalol obtained from the Standard solution. Not more than 0.3% each of sotalol hydrochloride related compound A and sotalol hydrochloride related compound B is found; not more than 0.4% of sotalol hydrochloride related compound C is 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 1.08 g of sodium 1-octanesulfonate to a 1000-mL volumetric flask. Dissolve in 10 mL of glacial acetic acid and about 70 mL of water. Add 720 mL of water, dilute with acetonitrile to volume, and mix. Filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).

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

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

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

Chromatographic system (see Chromatography 621)— 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 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak areas as directed for Procedure: the relative retention times are about 1.0 for sotalol and 0.39 for 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 25 µL) of the Standard preparation and the Assay preparation into 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 C is the concentration, in mg per mL, of USP Sotalol Hydrochloride RS in the Standard preparation; and RU and RS are the peak area ratios of sotalol to caffeine obtained from the Assay preparation and the Standard preparation, respectively.