Nicotine

(Ph Eur monograph 1452)

C10H14N2 162.2 54-11-5

Ph Eur

Definition
Nicotine contains not less than 99.0 per cent and not more than the equivalent of 101.0 per cent of 3[(2S)-1-methylpyrrolidin-2-yl]pyridine, calculated with reference to the anhydrous substance.
Characters
A colourless or brownish viscous liquid, volatile, hygroscopic, soluble in water, miscible with ethanol.
Identification
A. It complies with the test for specific optical rotation (see Tests).
B. Examine by infrared absorption spectrophotometry (2.2.24), comparing with the Ph. Eur. reference
spectrum of nicotine.
Tests
Appearance of solution
Dissolve 1.0 g in water R and dilute to 10 ml with the same solvent. The solution is clear (2.2.1) and not
more intensely coloured than reference solution Y5, BY5 or R5 (2.2.2, Method II).
Specific optical rotation (2.2.7)
Dissolve 1.00 g in ethanol R and dilute to 50.0 ml with the same solvent. The specific optical rotation is
-140 to -152.
Related substances
Examine by liquid chromatography (2.2.29).
Test solution
Dissolve 20.0 mg of the substance to be examined in the mobile phase and dilute to 25.0 ml with the
mobile phase.

Reference solution (a)

Dissolve 4 mg of nicotine ditartrate CRS and 2 mg of myosmine R in the mobile phase and dilute to 50.0
ml with the mobile phase.
Reference solution (b)
Dilute 0.4 ml of the test solution to 100.0 ml with the mobile phase.
The chromatography may be carried out using:
a stainless steel column 0.10 m long and 8 mm in internal diameter, packed with octadecylsilyl silica gel
for chromatography R (4 mm),
as mobile phase at a flow rate of 1.5 ml/min a solution prepared as follows: dissolve 2.31 g of sodium
dodecyl sulphate R in a mixture of 250 ml of acetonitrile R and 750 ml of a 13.6 g/l solution of potassium
dihydrogen phosphate R, adjusted to pH 4.5 with sodium hydroxide R or phosphoric acid R,
as detector a spectrophotometer set at 254 nm.
Inject 25 ml of reference solution (a). When the chromatograms are recorded in the prescribed conditions
the retention times are: nicotine about 13 min and impurity D about 11 min. The test is not valid unless the
resolution between the impurity D peak eluting closest to the nicotine peak and the peak due to nicotine is
at least 1.5; if necessary, adjust the concentration of acetonitrile in the mobile phase.
Adjust the sensitivity of the system so that the height of the principal peak in the chromatogram obtained
with 25 ml of reference solution (b) is at least 50 per cent of the full scale of the recorder.
Inject 25 ml of the test solution and 25 ml of reference solution (b). Continue the chromatography for twice
the retention time of the principal peak. In the chromatogram obtained with the test solution: the area of
any peak, apart from the principal peak, is not greater than the area of the principal peak in the
chromatogram obtained with reference solution (b) (0.4 per cent); the sum of the areas of all the peaks,
apart from the principal peak, is not greater than twice the area of the principal peak in the chromatogram
obtained with reference solution (b) (0.8 per cent). Disregard any peak with an area less than 0.1 times
the area of the principal peak in the chromatogram obtained with reference solution (b).
Water (2.5.12)
Not more than 0.5 per cent, determined on 1.00 g by the semi-micro determination of water.
Assay
Dissolve 60.0 mg in 30 ml of anhydrous acetic acid R. Titrate with 0.1M perchloric acid determining the
end-point potentiometrically (2.2.20).
1 ml of 0.1M perchloric acid is equivalent to 8.11 mg of C10H14N2.
Storage
Store, under nitrogen, in an airtight container , protected from light.
Impurities

A.

(2S)-1,2,3,6-tetrahydro-2,3-bipyridyl (anatabine),

B.

3-(1-methyl-1H-pyrrol-2-yl)pyridine (b-nicotyrine),

C.

(5S)-1-methyl-5-(pyridin-3-yl)pyrrolidin-2-one (cotinine),

D.

3-(4,5-dihydro-3H-pyrrol-2-yl)pyridine (myosmine),

E.

(1RS,2S)-1-methyl-2-(pyridin-3-yl)pyrrolidine 1-oxide (nicotine N-oxide).

Ph Eur
Action and use
Aid to smoking cessation.