Vecuronium Bromide

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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C₃₄H₅₇BrN₂O₄              ^▲637.74_{▲(USP 1-May-2021)}

Piperidinium, 1-[(2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(1-piperidinyl)androstan-16-yl]-1-methyl-, bromide;

^▲1-(30,17β-Dihydroxy-2β-piperidino-5α-androstan-16β-yl)-1-methylpiperidinium bromide, diacetate; 1-[3α,17β-Bis(acetyloxy)-2β-(piperidin-1-yl)-5α-androstan-16β-yl]-1-methylpiperidin-1-ium bromide _{▲(USP 1-May-2021)}         CAS RN^®: 50700-72-6; UNII: 7E4PHP5N1D.

1 DEFINITION

Vecuronium Bromide contains NLT 98.0% and NMT 102.0% of vecuronium bromide (C₃₄H₅₇BrN₂O₄), calculated on the dried basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

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

3 ASSAY

Change to read:

PROCEDURE

Solution A: Dissolve 8.0 g of sodium perchlorate in 6.0 mL of water, and dilute with acetonitrile to 1 L.

Solution B: Dissolve 1.6 g of ammonium chloride in 8 mL of ammonium hydroxide, and dilute with methanol to 1 L. [NOTE-Avoid excessive degassing to prevent the loss of ammonium hydroxide.]

Mobile phase: Solution A and Solution B (60:40)

Diluent: Transfer 1.0 mL of 1 N hydrochloric acid VS into a 1000-mL volumetric flask, and dilute with acetonitrile to volume.

Standard solution: 0.5 mg/mL of USP Vecuronium Bromide RS in Diluent

Sample solution: 0.5 mg/mL of Vecuronium Bromide in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm x 25-cm; 5-µm packing L3

Column temperature: 40°

Flow rate: 0.5 mL/min

Injection volume: 20 µL

^▲Run time: NLT 2.5 times the retention time of vecuronium bromide_{▲(USP 1-May-2021)}

System suitability

Sample: Standard solution

Suitability requirements

^▲Tailing factor: NMT 1.5_{▲(USP 1-May-2021)}

Relative standard deviation: NMT ^▲0.73%_{▲(USP 1-May-2021)}

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of vecuronium bromide (C₃₄H₅₇BrN₂O₄) in the portion of Vecuronium Bromide taken: 

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution 

C_S = concentration of USP Vecuronium Bromide RS in the Standard solution (mg/mL)

C_U = concentration of Vecuronium Bromide in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

Change to read:

ORGANIC IMPURITIES

Cation suppressor regeneration solution: 0.02 M tetrabutylammonium hydroxide

Mobile phase: [NOTE-Filter components before combining. Avoid evaporation of tetrahydrofuran during degassing.] Combine methanol, water. and bydrochloric acid (250:1500:1). Leave at room temperature for a few minutes. Add 45 mL of tetrahydrofuran, and then dilute with water to 2 L.

^▲Diluent: 2.5 mM hydrochloric acid_{▲(USP 1-May-2021)}

[NOTE-This applies to all of the solution preparations. The addition, with sonication of a small amount of acetonitrile (NMT 0.5 mL per 25 mg) to the weighed quantity of the samples may be used to aid in dissolution. Shaking and sonication may also be used after the addition of the required amount of ^▲Diluent_{▲(USP 1-May-2021)}]

System suitability solution: 5 µg/mL each of USP Vecuronium Bromide RS, USP Pancuronium Bromide RS, USP Vecuronium Bromide Related Compound A RS, USP Vecuronium Bromide Related Compound B RS. USP Vecuronium Bromide Related Compound C RS, and USP Vecuronium Bromide Related Compound F.RS in ^▲Diluent_{▲(USP 1-May-2021)}

Standard solution: 0.005 mg/ml. of USP Vecuronium Bromide RS in ^▲Diluent_{▲(USP 1-May-2021)}

Sample solution: 1 mg/mL of Vecuronium Bromide prepared as follows. To 25 mg of Vecuronium Bromide in a 25-mL volumetric flask add 0.5 mL of acetonitrile, sonicate, and rapidly dilute with Diluent.

Blank: ^▲Diluent_{▲(USP 1-May-2021)}

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: Conductivity with 4-mm cation suppressor

Column: 4.6-mm x 25-cm; 5-µm packing L1

Flow rates

Column: 1.5 mL/min

Cation suppressor: 2 mL/min

Injection volume: 25 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The system may need equilibration for 4 h. Rinse and store the column in acetonitrile and water (50:50).]

Suitability requirements

Peak-to-valley ratio: NLT 2.0 between the vecuronium bromide related compound F peak and the height of the trough between the vecuronium bromide related compound F and pancuronium peaks, System suitability solution

Relative standard deviation: NMT 10.0% for 3 replicate injections, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Vecuronium Bromide taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of USP Vecuronium Bromide RS from the Standard solution

C_S = concentration of USP Vecuronium Bromide RS in the Standard solution (mg/mL)

C_U = concentration of Vecuronium Bromide in the Sample solution (mg/mL)

F = relative response factor ^▲_{▲(USP 1-May-2021)} (see Table 1)

Acceptance criteria: See Table 1.

Table 1

5 SPECIFIC TESTS

Change to read:

5.1 OPTICAL ROTATION (781S), Procedures. Specific Rotation

Sample solution: 10 mg/mL ^▲of Vecuronium Bromide_{▲(USP 1-May-2021)} in dehydrated alcohol

Acceptance criteria: -16° to -20° at 20°

Change to read:

5.2 BACTERIAL, ENDOTOXINS TEST (85)

^▲Where the label states that vecuronium bromide must be subjected to further processing during the preparation of injectable dosage forms, the level of bacterial endotoxin is such that the requirement under the relevant dosage form monograph(s) in which vecuronium bromide is used can be met._{▲(USP 1-May-2021)}

5.3 LOSS ON DRYING (731)

Analysis: Dry at 105° for 2 h..

Acceptance criteria: NMT 2.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and store at room temperature.

Add the following:

LABELING: Where Vecuronium Bromide must be subjected to further processing during the preparation of injectable dosage forms, the label states that it is sterile or must be subjected to further processing, to ensure acceptable levels of bacterial endotoxins, it is so labeled._{▲ (USP 1-May-2021)}

Change to read:

USP REFERENCE STANDARDS (11)

USP Pancuronium Bromide RS

^▲_{▲(USP 1-May-2021)}

USP Vecuronium Bromide RS

USP Vecuronium Bromide Related Compound A. RS

3α,17β-diacetyl-oxy-23,16β-bispiperidinyl-5α-androstan;

^▲Also known as 2β,16β-Di(piperidin-1-yl)-50-androstane-3α,17β-diyl diacetate._{▲(USP 1-May-2021)}

C₃₃H₅₄N₂O₄       ^▲542.81_{▲(USP 1-May-2021)}

USP Vecuronium Bromide Related Compound B RS

Piperidinium, 1-[(2β,3α, 5α, 16β,17β)-3-acetyloxy-17-hydroxy-2-(1-piperidinyl) androstan-16-yl]-1-methyl bromide;

^▲Also known as 1-[3α-(Acetyloxy)-17β-hydroxy-2β-(piperidin-1-yl)-5α-androstan-16β-yl]-1-methylpiperidin-1-ium bromide_{▲(USP 1-May-2021)}

C₃₂H₅₅BrN₂O₃       ^▲595.71_{▲(USP 1-May-2021)}

USP Vecuronium Bromide Related Compound C RS

Piperidinium, 1-[(2β,3α,5α,16β,17β)-3,17-dihydroxy-2-(1-piperidinyl) androstan-16-yl]-1-methyl bromide;

^▲Also known as 1-[3a,17ẞ-Dihydroxy-23-(piperidin-1-yl)-5a-androstan-16ẞ-yl]-1-methylpiperidin-1-ium bromide_{▲(USP 1-May-2021)}

C₃₀H₅₃BrN₂O₂           ^▲553.67_{▲(USP 1-May-2021)}

USP Vecuronium Bromide Related Compound F. RS

Piperidinium, 1-[(2β,3α, 5α,16β,17β)-17-acetyloxy-3-hydroxy-2-(1-piperidinyl) androstan-16-yl]-1-methyl bromide;

^▲Also known as 1-[17α-(Acetyloxy)-3β-hydroxy-2β-(piperidin-1-yl)-5α-androstan-16β-yl]-1-methylpiperidin-1-ium bromide._{▲(USP 1-May-2021)}

C₃₂H₅₃BrN₂O₃          ^▲595.71_{▲(USP 1-May-2021)}