Adrenaline EUROPEAN PHARMACOPOEIA 11.

Limits : 01/2023:2303
– any impurity : not more than the area of the principal peak
in the chromatogram obtained with reference solution (b)
(0.1 per cent),
– total : not more than 5 times the area of the principal peak
in the chromatogram obtained with reference solution (b) ADRENALINE
(0.5 per cent),
– disregard limit : 0.5 times the area of the principal peak in Adrenalinum
the chromatogram obtained with reference solution (b)
(0.05 per cent).
Chlorides (2.4.4): maximum 200 ppm.
Dilute 2.5 mL of solution S to 15 mL with water R.
Nitrates : maximum 30 ppm. C9H13NO3 Mr 183.2
[51-43-4]
To 1 mL of solution S add 2 mL of concentrated ammonia R,
0.5 mL of a 10 g/L solution of manganese sulfate R, 1 mL of a DEFINITION
10 g/L solution of sulfanilamide R and dilute to 20 mL with 4-[(1R)-1-Hydroxy-2-(methylamino)ethyl]benzene-1,2-diol.
water R. Add 0.10 g of zinc powder R and cool in iced water
for 30 min ; shake from time to time. Filter and cool 10 mL of Synthetic product.
the filtrate in iced water. Add 2.5 mL of hydrochloric acid R1 Content : 99.0 per cent to 101.0 per cent (anhydrous substance).
and 1 mL of a 10 g/L solution of naphthylethylenediamine
CHARACTERS
dihydrochloride R. Allow to stand at room temperature. After
15 min the mixture is not more intensely coloured than a Appearance : white or almost white crystalline powder,
standard prepared at the same time and in the same manner, becoming coloured on exposure to air and light.
using 1.5 mL of nitrate standard solution (2 ppm NO3) R Solubility : practically insoluble in water, in ethanol (96 per
instead of 1 mL of solution S. The test is invalid if a blank cent) and in methylene chloride. It dissolves in hydrochloric
solution prepared at the same time and in the same manner, acid.
using 1 mL of water R instead of 1 mL of solution S, is more
intensely coloured than a 2 mg/L solution of potassium IDENTIFICATION
permanganate R. A. Infrared absorption spectrophotometry (2.2.24).
Sulfates (2.4.13) : maximum 500 ppm. Comparison : adrenaline CRS.
B. Specific optical rotation (see Tests).
Dilute 3 mL of solution S to 15 mL with distilled water R.
Iron (2.4.9): maximum 10 ppm, determined on solution S. TESTS
Loss on drying (2.2.32) : maximum 0.2 per cent, determined Solution S. Dissolve 1.000 g in a 25.75 g/L solution of
on 1.000 g by drying in an oven at 105 °C. hydrochloric acid R and dilute to 50.0 mL with the same
solvent. Examine the solution immediately.
Sulfated ash (2.4.14) : maximum 0.1 per cent.
Appearance of solution. Solution S is not more opalescent
Melt 1.0 g completely over a gas burner, then ignite the melted than reference suspension II (2.2.1) and not more intensely
substance with the burner. After ignition, lower or remove the coloured than reference solution BY5 (2.2.2, Method II).
flame in order to prevent the substance from boiling and keep Specific optical rotation (2.2.7): − 54.0 to − 50.0 (anhydrous
it burning until completely carbonised. Carry out the test for substance), determined on solution S.
sulfated ash using the residue.
Related substances. Liquid chromatography (2.2.29). Prepare
the solutions protected from light.
ASSAY
Solvent mixture A. Dissolve 5.0 g of potassium dihydrogen
Dissolve 60.0 mg in 50 mL of water R. Add 0.2 mL of phosphate R and 2.6 g of sodium octanesulfonate R in water
phenolphthalein solution R and titrate with 0.1 M sodium for chromatography R and dilute to 1000 mL with the same
hydroxide. solvent (it is usually necessary to stir for at least 30 min
1 mL of 0.1 M sodium hydroxide is equivalent to 7.31 mg of to achieve complete dissolution). Adjust to pH 2.8 with
C6H10O4. phosphoric acid R.
Solvent mixture B : acetonitrile R, solvent mixture A
IMPURITIES (13:87 V/V).
Solvent mixture C : 10.3 g/L solution of hydrochloric acid R,
solvent mixture B (10:90 V/V).
Test solution. Dissolve 40.0 mg of the substance to be
examined in 5 mL of a 10.3 g/L solution of hydrochloric acid R
A. pentanedioic acid (glutaric acid), and dilute to 50.0 mL with solvent mixture B.
Reference solution (a). Dilute 1.0 mL of the test solution
to 100.0 mL with solvent mixture B. Dilute 1.0 mL of this
solution to 10.0 mL with solvent mixture B.
Reference solution (b). Dissolve 1.5 mg of noradrenaline
tartrate CRS (impurity B) and 1.5 mg of adrenalone
B. butanedioic acid (succinic acid), hydrochloride R (impurity C) in solvent mixture B, add
1 mL of the test solution and dilute to 100 mL with solvent
mixture B.
Reference solution (c). Dissolve the contents of a vial of
adrenaline impurity mixture CRS (containing impurities D
C. heptanedioic acid (pimelic acid). and E) in 1 mL of solvent mixture C.

1886 See the information section on general monographs (cover pages)

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EUROPEAN PHARMACOPOEIA 11.0 Adrenaline tartrate

Reference solution (d). Dissolve the contents of a vial of STORAGE

adrenaline impurity F CRS in 1 mL of a 10.3 g/L solution of Under nitrogen, protected from light.
hydrochloric acid R.
Column : IMPURITIES
– size : l = 0.10 m, Ø = 4.6 mm ; Specified impurities : B, C, D, E, F.
– stationary phase : base-deactivated end-capped octadecylsilyl
silica gel for chromatography R (3 μm) ;
– temperature : 50 °C.
Mobile phase :
– mobile phase A : acetonitrile R1, solvent mixture A B. 4-[(1R)-2-amino-1-hydroxyethyl]benzene-1,2-diol
(5:95 V/V) ; (noradrenaline),
– mobile phase B : acetonitrile R1, solvent mixture A
(45:55 V/V) ;
Time Mobile phase A Mobile phase B
(min) (per cent V/V) (per cent V/V)
0 - 15 92 → 50 8 → 50
C. 1-(3,4-dihydroxyphenyl)-2-(methylamino)ethan-1-one
15 - 20 50 → 92 50 → 8
(adrenalone),
20 - 25 92 8

Flow rate : 2.0 mL/min.

Detection : spectrophotometer at 210 nm.
Injection : 20 μL.
Identification of impurities : use the chromatogram obtained
with reference solution (b) to identify the peaks due to
impurities B and C ; use the chromatogram supplied with D. 4-[(1R)-2-[benzyl(methyl)amino]-1-hydroxyethyl]ben-
adrenaline impurity mixture CRS and the chromatogram zene-1,2-diol,
obtained with reference solution (c) to identify the peaks due
to impurities D and E ; use the chromatogram obtained with
reference solution (d) to identify the peak due to impurity F.
Relative retention with reference to adrenaline
(retention time = about 4 min) : impurity F = about 0.2 ;
impurity B = about 0.8 ; impurity C = about 1.3 ;
impurity D = about 3.3 ; impurity E = about 3.7.
System suitability : reference solution (b) : E. 2-[benzyl(methyl)amino]-1-(3,4-dihydroxyphenyl)ethan-
– resolution : minimum 3.0 between the peaks due to 1-one,
impurity B and adrenaline.
Limits :
– correction factors : for the calculation of content,
multiply the peak areas of the following impurities by
the corresponding correction factor : impurity D = 0.7 ;
F. (1R)-1-(3,4-dihydroxyphenyl)-2-(methylamino)ethane-1-
impurity E = 0.6 ;
sulfonic acid.
– impurities B, C, F : for each impurity, not more than
twice the area of the principal peak in the chromatogram 01/2008:0254
obtained with reference solution (a) (0.2 per cent) ;
– impurities D, E : for each impurity, not more than the area
of the principal peak in the chromatogram obtained with
reference solution (a) (0.1 per cent) ;
– unspecified impurities : for each impurity, not more than the
area of the principal peak in the chromatogram obtained ADRENALINE TARTRATE
with reference solution (a) (0.10 per cent) ;
– total : not more than 5 times the area of the principal peak Adrenalini tartras
in the chromatogram obtained with reference solution (a)
(0.5 per cent) ;
– disregard limit : 0.5 times the area of the principal peak in
the chromatogram obtained with reference solution (a)
(0.05 per cent).
C13H19NO9 Mr 333.3
Water (2.5.32) : maximum 0.4 per cent, determined on 0.300 g [51-42-3]
using the evaporation technique at 130 °C.
Sulfated ash (2.4.14) : maximum 0.1 per cent, determined on DEFINITION
1.0 g. (1R)-1-(3,4-Dihydroxyphenyl)-2-(methylamino)ethanol
hydrogen (2R,3R)-2,3-dihydroxybutanedioate.
ASSAY Content : 98.5 per cent to 101.0 per cent (dried substance).
Dissolve 0.150 g in 50 mL of anhydrous acetic acid R. Titrate
with 0.1 M perchloric acid, determining the end-point CHARACTERS
potentiometrically (2.2.20). Appearance : white or greyish-white, crystalline powder.
1 mL of 0.1 M perchloric acid is equivalent to 18.32 mg Solubility : freely soluble in water, slightly soluble in ethanol
of C9H13NO3. (96 per cent).

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