Bretylium Tosylate Injection

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

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

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Bretylium Tosylate Injection is a sterile solution of Bretylium Tosylate in Water for Injection. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of C₁₈H₂₄BrNO₃S.

Packaging and storage-Preserve in single-dose containers, preferably of Type I glass.

USP REFERENCE STANDARDS (11)

USP Bretyllum Tosydate RS

1 Identification

The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that of the Standard preparation, both relative to the internal standard, as obtained in the Assay.

BACTERIAL ENDOTOXINS TEST (85). It contains not more than 0.20 USP Endotoxin Unit per mg of bretylium tosylate.

PH (791): between 3.5 and 7.0.

PARTICULATE MATTER IN INJECTIONS (788): meets the requirements for small-volume injections.

Other requirements-It meets the requirements under Injections and Implanted Drug Products (1).

2 Assay

pH 3.1 Tetramethylammonium phosphate buffer-Dissolve 1.38 g of monobasic sodium phosphate and 2.0 mL of 25% tetra-methylammonium hydroxide solution in methanol in 800 mL of water, adjust with phosphoric acid to a pH of 3.1 ± 0.1, dilute with water to 1000 ml, and mix.

Mobile phase-Transfer 15 mL of tetrahydrofuran and 75 ml of acetonitrile to a 1000-mL volumetric flask, and dilute with pH 3.1

Tetramethylammonium phosphate buffer to volume.

Standard preparation-Dissolve an accurately weighed quantity of USP Bretylium Tosylate RS in water, and dilute quantitatively, and stepwise if necessary, with water to obtain a solution having a known concentration of about 0.2 mg per mL

Assay preparation-Transfer an accurately measured volume of Injection, equivalent to about 10 mg of bretylium tosylate, to a 50-ml volumetric flask, dilute with water to volume, and mix.

Chromatographic system (see Chromatography (621))-The liquid chromatograph is equipped with a 220-nm detector and a 3.9 - mm * 30 - 1 cm column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for tosylate and 1.0 for bretylium; the resolution, R, between the bretylium and tosylate peaks is not less than 3.0; and the relative standard deviation for replicate injections is not more than 1.4%. Procedure-Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C₁₈H₂₄BrNO₃S in each mL of the Injection taken by the formula:

50(C/V)(r_u /r_s )

in which C is the concentration, in mg per mL, of USP Bretylium Tosylate RS in the Standard preparation; V is the volume, in mL, of Injection taken; and r_u and r_s are the bretylium peak responses obtained from the Assay preparation and the Standard preparation, respectively.