Sotalol Hydrochloride

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

1 DEFINITION

Sotalol Hydrochloride contains NLT 98.5% and NMT 101.5% of sotalol hydrochloride (C₁₂H₃₀N₂O₃S · HCl).

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉 , Infrared Spectroscopy: 197K

B. The retention time of the sotalol peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

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 and dilute with acetonitrile to volume.

Diluent: Acetonitrile and water (1:4)

Internal standard solution: 4.5 mg/mL of caffeine in Diluent

Standard stock solution: 2 mg/mL of USP Sotalol Hydrochloride RS in Diluent

Standard solution: 0.2 mg/mL of USP Sotalol Hy drochloride RS prepared as follows. Transfer 10.0 mL of Standard stock solution and 5.0 mL of Internal standard solution to a 100-mL volumetric flask. Dilute with Diluent to volume.

Sample stock solution: 2 mg/mL of Sotalol Hydrochloride in Diluent

Sample solution: 0.2 mg/mL of Sotalol Hydrochloride prepared as follows. Transfer 10 mL of Sample stock solution and 5.0 mL of Internal standard solution to a 100-mL volumetric flask. Dilute with Diluent to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 238 nm

Column: 3.9-mm × 30-cm; 10-µm packing L1

Flow rate: 1.5 mL/min

Injection volume: 25 µL

System suitability

Sample: Standard solution

[NOTE—The relative retention times for caffeine and sotalol are 0.39 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 8.5 between caffeine and sotalol Relative standard deviation: NMT 0.55%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of sotalol hydrochloride (C₁₂H₃₀N₂O₃S · HCl) in the portion of Sotalol Hydrochloride taken:

Result = (R_U/R_S) × (C_S/C_U) × 100

R_U = peak area ratio of sotalol to caffeine from the Sample solution

R_S = peak area ratio of sotalol to caffeine from the Standard solution

C_S = concentration of USP Sotalol Hydrochloride RS in the Standard solution (mg/mL)

C_U = concentration of Sotalol Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.5%–101.5%

4 IMPURITIES

RESIDUE ON IGNITION 〈281〉: NMT 0.5%

ORGANIC IMPURITIES

Mobile phase and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 6 µg/mL each 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

Sample solution: 2 mg/mL of Sotalol Hydrochloride in Mobile phase

System suitability

Sample: Standard solution

[NOTE—See Table 1 for relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between sotalol related compound A and sotalol Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each sotalol related compound in the portion of Sotalol Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of the corresponding sotalol related compound from the Sample solution

r_S = peak response of the corresponding sotalol related compound from the Standard solution

C_S = concentration of the corresponding Reference Standard in the Standard solution (µg/mL)

C_U = concentration of Sotalol Hydrochloride in the Sample solution (µg/mL)

Calculate the percentage of any unspecified impurity in the portion of Sotalol Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each unspecified impurity from the Sample solution

r_S = peak response of sotalol from the Standard solution

C_S = concentration of USP Sotalol Hydrochloride RS in the Standard solution (µg/mL)

C_U = concentration of Sotalol Hydrochloride in the Sample solution (µg/mL)

Acceptance criteria: See Table 1.

Table 1

5 SPECIFIC TESTS

CONTENT OF CHLORIDE

Sample: 310 mg

Titrimetric system

Mode: Direct titration

Titrant: 0.1 N silver nitrate VS Endpoint detection: Potentiometric

Analysis: Transfer the Sample to a glass beaker, and dissolve in 100 mL of water and 10 mL of glacial acetic acid. Titrate with Titrant, and determine the endpoint potentiometrically. Each milliliter of Titrant is equivalent to 3.545 mg of chloride (Cl).

Acceptance criteria: 11.1%–11.9%

OPTICAL ROTATION 〈781S〉 , Procedures, Specific Rotation Sample solution: 125 mg/mL in methanol

Acceptance criteria: −0.7° to +0.7°

WATER DETERMINATION 〈921〉 , Method I: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers. Store at controlled room temperature.

Change to read:

USP REFERENCE STANDARDS 〈11〉

USP Sotalol Hydrochloride RS

USP Sotalol Related Compound A RS

N-[4-(Isopropylglycyl)phenyl]methanesulfonamide hydrochloride. C₁₂H₁₈N₂O₃S · HCl    306.81

USP Sotalol Related Compound B RS

N-(4-Formylphenyl)methanesulfonamide. C₈H₉NO₃S    199.22

USP Sotalol Related Compound C RS

N-{4-[2-(Isopropylamino)ethyl]phenyl}methanesulfonamide hydrochloride. C₁₂H₃₀N₂O₃S · HCl    292.82 (CN 1-Aug-2024)