Pancuronium Bromide

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

C₃₅H₆₀Br₂N₂O₄ 732.67

Piperidinium, 1,1'-[(2β,3α,5α,16β,17β)-3,17-bis(acetyl oxy)androstane-2,16-diyl]bis[1-methyl]-, dibromide;

1,1'-(3α,17β-Dihydroxy-5α-androstan-2β,16β-ylene)bis[1-methylpiperidinium] dibromide diacetate;

2β,16β-Dipiperidino-5α-androstane-3α,17β-diol diacetate dimethobromide CAS RN^®: 15500-66-0; UNII: U9LY9Y75X2.

1 DEFINITION

Pancuronium Bromide contains NLT 98.0% and NMT 102.0% of pancuronium bromide (C₃₅H₆₀Br₂N₂O₄), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

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

C. IDENTIFICATION TESTS-GENERAL (191), Bromide: A solution (1 in 10) meets the requirements of test B.

3 ASSAY

3.1 PROCEDURE

Diluent: 0.0024 M hydrochloric acid

Mobile phase: Acetonitrile, methanol, and 0.024 M hydrochloric acid (125:200:675)

Standard stock solution: 1.0 mg/mL prepared as follows. Transfer the required quantity of USP Pancuronium Bromide RS to a suitable volumetric flask. Dissolve in 2% of the flask volume of acetonitrile, dilute with Diluent to volume, and sonicate for 3 min.

Standard solution: 0.1 mg/mL of USP Pancuronium Bromide RS in Diluent, from the Standard stock solution

Sample stock solution: 1.0 mg/mL prepared as follows. Transfer the required quantity of Pancuronium Bromide to a suitable volumetric flask. Dissolve in 2% of the flask volume of acetonitrile, dilute with Diluent to volume, and sonicate for 3 min.

Sample solution: 0.1 mg/mL of Pancuronium Bromide in Diluent, from the Sample stock solution

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: Conductivity with suppression

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

Temperatures

Column: 35°

Detector: 40°

Suppressor: 4-mm cationic membrane suppressor or equivalent

Suppression solution: 0.15 M tetrabutylammonium hydroxide

Suppressor flow rate: 1 mL/min

Flow rate: 0.75 mL/min

Injection volume: 25 µL

Run time: 2 times the retention time of pancuronium

3.3 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of pancuronium bromide (C₃₅H₆₀Br₂N₂O₄) in the portion of Pancuronium Bromide taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

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

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

Diluent, Mobile phase, Standard stock solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 1 mg/mL of USP Pancuronium Bromide RS and 0.02 mg/mL each of USP Pancuronium Bromide Related Compound A RS, USP Pancuronium Bromide Related Compound B RS, USP Pancuronium Bromide Related Compound C RS, and USP Vecuronium Bromide RS, prepared as follows. Transfer the required amounts of the individual components to a suitable volumetric flask. Dissolve in 2% of the flask volume of acetonitrile, dilute with Diluent to volume, and sonicate for 3 min.

Standard solution: 0.01 mg/mL of USP Pancuronium Bromide RS in Diluent, from the Standard stock solution

Sample solution: 1.0 mg/mL prepared as follows. Transfer the required quantity of Pancuronium Bromide to a suitable volumetric flask. Dissolve in 2% of the flask volume of acetonitrile, dilute with Diluent to volume, and sonicate for 3 min.

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between pancuronium related compound B and pancuronium related compound A, and NLT 1.5 between the pancuronium related compound C and vecuronium peaks, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 10.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity, including any unspecified impurity, in the portion of Pancuronium Bromide taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of pancuronium from the Standard solution

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

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

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a Piperidinium, 1-[(2,3,5,16,17)-17-acetyloxy-3-hydroxy-2-(1-piperidinyl)androstan-16-yl]-1-methyl. This impurity is an acid degradation product of vecuronium bromide and not that of pancuronium bromide.

5 SPECIFIC TESTS

5.1 OPTICAL ROTATION, Specific Rotation (781S)

Sample solution: 30 mg/mL in water

Acceptance criteria: +39° to +43°

5.2 WATER DETERMINATION, Method I (921)

NMT 8.0%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight containers, protected from light and moisture.

6.2 USP REFERENCE STANDARDS (11)

USP Pancuronium Bromide RS

USP Pancuronium Bromide Related Compound A RS

1,1'-(3α,17β-Dihydroxy-5α-androstan-28,16β-ylene) bis(1-methylpiperidinium) dibromide.

C₃₁H₅₆Br₂N₂O₂ 648.60

USP Pancuronium Bromide Related Compound B RS

1,1'-(17ẞ-Acetoxy-3a-hydroxy-5a-androstan-2ẞ,16ẞ-ylene) bis(1-methylpiperidinium) dibromide.

C₃₃H₅₈Br₂N₂O₃ 690.63

USP Pancuronium Bromide Related Compound C RS

1,1'-(3α-Acetoxy-17β-hydroxy-5α-androstan-2β,16β-ylene) bis(1-methylpiperidinium) dibromide.

C₃₃H₅₈Br₂N₂O₃ 690.63

USP Vecuronium Bromide RS