Bupivacaine Hydrochloride 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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1 DEFINITION

Bupivacaine Hydrochloride Injection is a sterile solution of Bupivacaine Hydrochloride in Water for Injection. It contains NLT 93.0% and NMT 107.0% of the labeled amount of bupivacaine hydrochloride (C₁₈H₂₈N₂O·HCl).

2 IDENTIFICATION

A. Identification—Organic Nitrogenous Bases 〈181〉

Sample solution: 2 mg/mL of bupivacaine hydrochloride in 0.01 N hydrochloric acid, from Injection

Analysis: Proceed as directed in the chapter beginning with “Transfer the liquid to a separator”.

Acceptance criteria: Meets the requirements

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

3 ASSAY

Change to read:

Procedure

Buffer: 1.94 g/L of monobasic potassium phosphate and 2.48 g/L of dibasic potassium phosphate in water. Adjust, if necessary, with 1 N potassium hydroxide or 1 M phosphoric acid to a pH of 6.8.

Mobile phase: Acetonitrile and Buffer (65:35). Adjust, if necessary, with 1 M phosphoric acid to a pH of 7.7 ± 0.2. Filter the solution through a membrane filter of 1-µm or finer pore size, and degas.

Internal standard solution: 1.3 mg/mL of dibutyl phthalate in methanol

Standard solution: 0.5 mg/mL of USP Bupivacaine Hydrochloride RS, prepared as follows. In a 100-mL volumetric flask, dissolve 50 mg of USP Bupivacaine Hydrochloride RS in 10.0 mL of water, using sonication if necessary. Add 10 mL of Internal standard solution, and dilute with methanol to volume.

Sample solution: Nominally 0.5 mg/mL of bupivacaine hydrochloride, prepared as follows. In a 100-mL volumetric flask, transfer an amount of Injection equivalent to 50 mg of bupivacaine hydrochloride, add 10.0 mL of Internal standard solution, and dilute with methanol to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 263 nm

Column: ▲3.9-mm▲ (ERR 1-May-2023) × 30-cm; packing L1

Flow rate: 2 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[Note—The relative retention times for bupivacaine ▲ ▲ (ERR 1-May-2023) and dibutyl phthalate are about 1.0 and 1.2, respectively.]

Suitability requirements

Resolution: NLT 2.0 between bupivacaine ▲ ▲ (ERR 1-May-2023) and dibutyl phthalate

Relative standard deviation: NMT 1.0% for the ▲peak response▲ (ERR 1-May-2023) ratio of bupivacaine to the internal standard from three replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of bupivacaine hydrochloride (C₁₈H₂₈N₂O·HCl) in the portion of Injection taken:

Result = (R₁/R₂) × (C₁/C₂) × 100

R₁ = peak response ratio of bupivacaine to the internal standard from the Sample solution

R₂ = peak response ratio of bupivacaine to the internal standard from the Standard solution

C₁ = concentration of USP Bupivacaine Hydrochloride RS, calculated on the anhydrous basis, in the Standard solution (mg/mL)

C₂ = nominal concentration of bupivacaine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 93.0%–107.0%

4 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: NMT 2.5 USP Endotoxin Units/mg of bupivacaine hydrochloride

pH 〈791〉: 4.0–6.5

Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉.

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or in multiple-dose containers, preferably of Type I glass. Injection labeled to contain 0.5% or less of bupivacaine hydrochloride may be packaged in 50-mL, multiple-dose containers.

USP Reference Standards 〈11〉

USP Bupivacaine Hydrochloride RS