Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Adrenoceptor agonist.
DEFINITION
Adrenaline Solution is an isotonic cutaneous solution containing 0.18% w/v of Adrenaline Acid Tartrate with a suitable combination of an antioxidant and an antimicrobial preservative in Purified Water.
The solution complies with the requirements stated under Liquids for Cutaneous Application and with the following requirements. Where appropriate, the solution also complies with the requirements stated under Unlicensed Medicine.
Content of adrenaline, C9H13NO3
0.09 to 0.11% w/v.
CHARACTERISTICS
A clear, colourless solution.
IDENTIFICATION
A. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is the same as that of the principal peak in the chromatogram obtained with solution (2).
B. To 1 mL add a 0.25% w/v solution of iron (III) chloride hexahydrate drop wise until a green colour is produced. On the gradual addition of sodium hydrogen carbonate solution, the solution changes first to blue and then to red.
C. To 10 mL add 2 mL of a 10% w/v solution of disodium hydrogen orthophosphate and sufficient iodinated potassium iodide solution to produce a brown colour. Remove excess iodine by adding 0.1M sodium thiosulfate drop wise; a red colour is produced.
TESTS
Acidity
pH, 2.7 to 3.6, Appendix V L.
Noradrenaline
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in the mobile phase.
(1) The preparation being examined.
(2) 0.0018% w/v of noradrenaline acid tartrate.
(3) 0.0018% w/v of noradrenaline acid tartrate and 0.0018% w/v of adrenaline acid tartrate BPCRS.
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 containing 4.0 g of tetramethylammonium hydrogen sulfate, 1.1 g of sodium heptanesulfonate and 2 mL of 0.1M disodium edetate in a mixture of 950 mL of water and 50 mL of methanol, the pH of the mixture being adjusted 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.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to noradrenaline is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in the mobile phase.
(1) Dilute 1 volume of the preparation being examined to 10 volumes.
(2) 0.02% w/v of adrenaline acid tartrate BPCRS.
(3) 0.02% w/v of adrenaline acid tartrate BPCRS and 0.02% w/v of noradrenaline acid tartrate.
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
Add 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 50 mL of methanol and 950 mL of water and adjust the pH of the mixture to 3.5 with 1M sodium hydroxide.
SYSTEM SUITABILITY
The Assay 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 preparation being examined using the declared content of C9H13NO3 in adrenaline acid tartrate BPCRS.
STORAGE
Adrenaline Solution should be kept in a well-filled glass container suitable for parenteral preparations, Appendix XIX B, and should be protected from light.
LABELLING
The label states (1) the date after which the solution is not intended to be used; (2) the conditions under which it should be stored.
The quantity of active ingredient is stated in terms of the equivalent amount of adrenaline (epinephrine).
The label indicates the pharmaceutical form as ‘cutaneous solution’.
Adrenaline Solution contains the equivalent of adrenaline (epinephrine), 1 in 1000 (1 mg in 1 mL).
When a solution of adrenaline hydrochloride is prescribed or demanded, a solution complying with the requirements of this monograph may be dispensed or supplied.
