Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Non-depolarizing neuromuscular blocker.
DEFINITION
Pancuronium Injection is a sterile solution of Pancuronium Bromide in Sodium Chloride Intravenous Infusion.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of pancuronium bromide, C35H60Br2N2O4
95.0 to 105.0% of the stated amount.
CHARACTERISTICS
A colourless liquid.
IDENTIFICATION
A. In the test for Related substances, the principal spot in the chromatogram obtained with solution (1) is similar in position, colour and size to the principal spot in the chromatogram obtained with solution (2).
B. To a volume containing 5 mg of Pancuronium Bromide, diluted if necessary to 10 mL with water, add 10 mL of 1,2- dichloroethane followed by 1 mL of methyl orange solution. Shake, centrifuge, allow the layers to separate and acidify the organic layer with 1M sulfuric acid. A red colour is produced.
C. Yields reaction A characteristic of bromides, Appendix VI.
TESTS
Acidity
pH, 3.8 to 4.2, Appendix V L.
Related substances
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Evaporate a volume of the injection containing 20 mg of Pancuronium Bromide to dryness in a current of nitrogen, add 2 mL of acetonitrile to the residue and mix with the aid of ultrasound for 1 minute.
(2) 1.0% w/v of pancuronium bromide BPCRS in acetonitrile.
(3) Dilute 1 volume of solution (1) to 50 volumes with acetonitrile.
(4) Dilute 1 volume of solution (3) to 2 volumes with acetonitrile.
(5) 3% w/v of pancuronium bromide for system suitability EPCRS (containing 1.0 per cent of impurity D) in methylene chloride.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel.
(b) Use the mobile phase as described below.
(c) Apply 5 µL of each solution.
(d) Develop the plate to 15 cm in an unsaturated tank.
(e) After removal of the plate, dry it in a current of cold air and spray with a 1% w/v solution of sodium nitrite in methanol. Allow to stand for 2 minutes, spray the plate with potassium iodobismuthate solution and dry in a current of cold air.
MOBILE PHASE
5 volumes of a 20% w/v solution of sodium iodide, 10 volumes of acetonitrile and 85 volumes of propan-2-ol.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (5) shows two distinct spots and the Rf value of the spot due to impurity D relative to that due to pancuronium bromide is at least 1.2.
LIMITS
In the chromatogram obtained with solution (1):
any spot corresponding to dacuronium bromide (impurity A) or vecuronium bromide (impurity D) is not more intense than the spot in the chromatogram obtained with solution (5) (3%). Impurity A and impurity D have the same Rf value and if present in the same solution would produce a single spot;
any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (3) (2%); not more than one such spot is more intense than the spot in the chromatogram obtained with solution (4) (1%).
ASSAY
To a volume containing 4 mg of Pancuronium Bromide add 1 mL of a 13.9% w/v solution of hydroxylamine hydrochloride followed by 1 mL of a 15% w/v solution of sodium hydroxide. Allow to stand for 10 minutes and then add 1 mL of a solution prepared by diluting hydrochloric acid with water to contain 12.76% w/v of HCl. Add 1 mL of a 10% w/v solution of iron(III) chloride in 0.1M hydrochloric acid, add sufficient water to produce 25 mL, centrifuge and measure the absorbance of the clear, supernatant liquid at the maximum at 510 nm, Appendix II B, using in the reference cell a solution prepared by carrying out the operation using an equal volume of water in place of the injection. Calculate the content of C35H60Br2N2O4 from the absorbance obtained by repeating the operation using a suitable quantity of pancuronium bromide BPCRS dissolved in water and using the declared content of C35H60Br2N2O4 in pancuronium bromide BPCRS.
STORAGE
Pancuronium Injection should be stored at a temperature of 2° to 8°.
