Atracurium Besylate 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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Atracurium besylate Injection

1 DEFINITION

Atracurium Besylate Injection is a sterile solution containing NLT 90.0% and NMT 115.0% of the labeled amount of atracurium besylate (C₆₅H₈₂N₂O₁₈S₂). It contains an amount of the trans-trans isomer equivalent to NLT 5.0% and NMT 6.5% of the labeled amount of atracurium besylate, an amount of the cis-trans isomer equivalent to NLT 34.5% and NMT 38.5% of the labeled amount of atracurium besylate, and an amount of the cis-cis isomer equivalent to NLT 55.0% and NMT 60.0% of the labeled amount of atracurium besylate.

[Note—The Injection is unstable at room temperature. Store all samples in the refrigerator. Analyze all preparations as soon as possible, or use a refrigerated injector.]

2 IDENTIFICATION

A. The retention times of the peaks of the three atracurium besylate isomers from the Sample solution correspond to those from the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer: 10.2 g of monobasic potassium phosphate in a 1000-mL volumetric flask. Dissolve in 950 mL of water. While stirring, adjust with phosphoric acid to a pH of 3.1, and dilute with water to volume.

Solution A: Acetonitrile, methanol, and Buffer (20:5:75)

Solution B: Acetonitrile, methanol, and Buffer (20:30:50)

Mobile phase: See Table 1.

Standard solution: 1 mg/mL of USP Atracurium Besylate RS in Solution A

Sample solution: Nominally equivalent to 1 mg/mL of atracurium besylate from Injection in Solution A

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.6-mm × 25-cm; 5-µm base-deactivated packing L1

Flow rate: 1 mL/min

Injection size: 20 µL

System suitability

Sample: Standard solution

[Note—Refer to Table 2 under Organic Impurities for relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between the atracurium trans-trans isomer and the cis-trans isomer peaks; NLT 1.5 between the atracurium cis-trans isomer and the cis-cis isomer peaks

Relative standard deviation: NMT 2.0%, for the cis-cis isomer peak

Analysis

Samples: Standard solution and Sample solution

Measure the responses for the three atracurium besylate isomer peaks.

Calculate the percentage of the labeled amount of atracurium besylate (C₆₅H₈₂N₂O₁₈S₂) in each mL of the Injection taken:

Result = (r_U / r_S) × (C_S / C_U) × 100

r_U = sum of the peak responses for the trans-trans isomer, the trans-cis isomer, and the cis-cis isomer from the Sample solution

r_S= sum of the peak responses for the trans-trans isomer, the trans-cis isomer, and the cis-cis isomer from the Standard solution

C_S = concentration of USP Atracurium Besylate RS in the Standard solution (mg/mL)

C_U= nominal concentration of atracurium besylate in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–115.0% of the labeled amount of atracurium besylate (C₆₅H₈₂N₂O₁₈S₂). It contains NLT 5.0% and NMT 6.5% of the trans-trans isomer, NLT 34.5% and NMT 38.5% of the cis-trans isomer, and NLT 55.0% and NMT 60.0% of the cis-cis isomer

4 IMPURITIES

Organic Impurities

Buffer, Solution A, Solution B, Mobile phase, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Standard stock solution: 1 mg/mL of USP Atracurium Besylate RS in Solution A

Standard solution: 0.02 mg/mL of USP Atracurium Besylate RS in Solution A, from Standard stock solution

System suitability

Sample: Standard solution

Resolution: NLT 1.5 between the atracurium trans-trans isomer and the cis-trans isomer peaks; NLT 1.5 between the atracurium cis-trans isomer and the cis-cis isomer peaks

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Sample solution taken:

Result = (r_U / r_S) × (C_S / C_U) × (1/F) × 100

r_U = peak response for each impurity from the Sample solution

r_S= sum of all the peak responses from the Standard solution

C_S = concentration of USP Atracurium Besylate RS in the Standard solution (mg/mL)

C_U= nominal concentration of atracurium besylate in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

ᵃ For identification purposes only.

ᵇ trans isomer of the hydroxy compound.

ᶜ cis isomer of the hydroxy compound.

ᵈ trans isomer of the monoacrylate.

ᵉ cis isomer of the monoacrylate.

ᶠ Impurity consists of two isomers that are separated under these conditions; integrate both peaks for the impurity calculations

5 SPECIFIC TESTS

pH 〈791〉: 3.00–3.65

Sterility Tests 〈71〉: It meets the requirements when tested as directed for Test for Sterility of the Product to Be Examined, Membrane Filtration.

Bacterial Endotoxins Test 〈85〉: It contains NMT 5.56 USP Endotoxin Units/mg of atracurium besylate.

Injections and Implanted Drug Products 〈1〉: Meets the requirements

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or multiple-dose containers, preferably of Type I glass, in a refrigerator, and protect from freezing. Protect from light.

USP Reference Standards 〈11〉

USP Atracurium Besylate RS