(Ph. Eur. 11.6 update)
Action and use
Local anaesthetic + class I antiarrhythmic; adrenoceptor agonist.
DEFINITION
Lidocaine and Adrenaline Injection is a sterile solution of Lidocaine Hydrochloride Monohydrate and Adrenaline Acid Tartrate in Water for Injections.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of lidocaine hydrochloride monohydrate, C14H22N2O,HCl,H2O
95.0 to 105.0% of the stated amount.
Content of adrenaline, C9H13NO3
87.5 to 112.5% of the stated amount.
CHARACTERISTICS
A colourless solution.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in water.
(1) Dilute a quantity of the injection, if necessary, to produce a solution containing 0.2% w/v of Lidocaine Hydrochloride Monohydrate.
(2) 0.2% w/v of lidocaine hydrochloride BPCRS.
(3) 0.2% w/v of each of lidocaine hydrochloride BPCRS and bupivacaine hydrochloride BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a silica gel precoated plate (Merck silica gel 60G plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 5 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry it in a current of cold air, heat at 110° for 1 hour, place the hot plate in a tank of chlorine gas prepared by the addition of hydrochloric acid to a 5% w/v solution of potassium permanganate contained in a beaker placed in the tank and allow to stand for 2 minutes. Dry the plate in a current of cold air until an area of the plate below the line of application gives at most a very faint blue colour with a 0.5% w/v solution of potassium iodide in starch mucilage; avoid prolonged exposure to cold air. Spray the plate with a 0.5% w/v solution of potassium iodide in starch mucilage.
MOBILE PHASE
5 volumes of methanol and 95 volumes of dichloromethane.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated principal spots.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (2).
B. In the Assay for adrenaline, the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).
Acidity
pH, 3.0 to 4.5, Appendix V L.
ASSAY
For lidocaine hydrochloride monohydrate
Make a quantity containing 0.1 g of Lidocaine Hydrochloride Monohydrate alkaline with 2M sodium hydroxide and extract with three 20-mL quantities of chloroform, washing each extract with the same 10 mL of water.
Filter the washed extracts through a filter paper moistened with chloroform and wash the filter with 10 mL of chloroform.
Add the washings to the filtrate and carry out Method I for non-aqueous titration, Appendix VIII A, using 0.02M perchloric acid VS as titrant and crystal violet solution as indicator.
Each mL of 0.02M perchloric acid VS is equivalent to 5.776 mg of C14H22N2O,HCl,H2O.
For adrenaline
Prepare a solution by adding 8.0 g of tetramethylammonium hydrogen sulfate, 2.2 g of sodium heptanesulfonate and 2 mL of 0.1M disodium edetate to a mixture of 900 mL of water and 100 mL of methanol, adjust the pH to 3.5 using 1M sodium hydroxide and filter through glass microfibre paper under reduced pressure (solution A).
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dilute the injection with solution A, if necessary, to contain 0.0005% w/v of adrenaline and dilute 5 mL of the resulting solution to 10 mL with solution A.
(2) Dilute 5 mL of a 0.001% w/v solution of adrenaline acid tartrate BPCRS to 10 mL with solution A.
(3) Mix 5 mL of solution (2) with 5 mL of a 0.001% w/v solution of noradrenaline acid tartrate in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 μm) (Nucleosil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 205 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
A solution prepared by adding 4.0 g of tetramethylammonium hydrogen sulfate, 1.1 g of sodium heptanesulfonate and 2 mL of 0.1M disodium edetate to a mixture of 950 mL of water and 50 mL of methanol and adjusting the pH to 3.5 with 1M sodium hydroxide.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the two principal peaks is at least 2.0.
DETERMINATION OF CONTENT
Calculate the content of C9H13NO3 in the injection using the declared content of C9H13NO3 in adrenaline acid tartrate BPCRS.
STORAGE
Lidocaine and Adrenaline Injection should be protected from light.
LABELLING
The quantity of Adrenaline Acid Tartrate is stated in terms of the equivalent amount of adrenaline (epinephrine).
