Identification—
B:
Thin-Layer Chromatographic Identification Test 
201
—
Test solution—
Dissolve a quantity of Sotalol Hydrochloride in methanol to obtain a solution having a concentration of about 2 mg per mL.
Developing solvent system:
a mixture of chloroform and methanol (70:30).
Procedure—
Proceed as directed in the chapter, except to place two 25-mL beakers, each containing about 10 mL of ammonium hydroxide, on the bottom of the chromatographic chamber that is lined with filter paper and contains the Developing solvent system, allow to equilibrate for 15 minutes, then place the plate in the chamber, and develop the chromatograms until the solvent front has moved about two-thirds of the length of the plate: meets the requirements.
Limit of methanol, isopropyl alcohol, and acetone—
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:
1000(C/W)(rU / rS),
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.
Related compounds—
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:
10(C/W)(ri / rS),
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:
10(C/W)(rsi / rS),
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.
Assay—
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 C
12H
20N
2O
3S·HCl in the portion of Sotalol Hydrochloride taken by the formula:
500C(RU / RS),
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.
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