(Ph. Eur. monograph 2599)
C18H26N2O12,2H2O 498.4 6019-06-3
Action and use
Aid to smoking cessation.
DEFINITION
3-[(2S)-1-Methylpyrrolidin-2-yl]pyridine bis[(2R,3R)-2,3-dihydroxybutanedioate] dihydrate.
Content
98.5 per cent to 101.5 per cent (anhydrous substance).
CHARACTERS
Appearance
White or almost white powder.
Solubility
Soluble in water and in ethanol (96 per cent).
IDENTIFICATION
Infrared absorption spectrophotometry (2.2.24).
Comparison: nicotine ditartrate dihydrate CRS.
TESTS
pH (2.2.3)
3.0 to 3.4.
Dissolve 1.0 g in carbon dioxide-free water R and dilute to 10 mL with the same solvent.
Specific optical rotation (2.2.7)
+ 21.0 to + 23.0.
Dissolve 0.25 g in water R and dilute to 25.0 mL with the same solvent.
Related substances
Liquid chromatography (2.2.29). Prepare the solutions immediately before use.
Test solution: Dissolve 60 mg of the substance to be examined in water R and dilute to 25.0 mL with the same solvent.
Reference solution (a): Dissolve the contents of a vial of nicotine for system suitability CRS (containing impurities A, B, C, D, E, F and G) in 1.0 mL of water R.
Reference solution (b) Dilute 1.0 mL of the test solution to 100.0 mL with water R. Dilute 1.0 mL of this solution to 10.0 mL with water R.
Column:
— size: l = 0.15 m, Ø = 4.6 mm;
— stationary phase: end-capped polar-embedded octadecylsilyl amorphous organosilica polymer R (5 μm).
Mobile phase:
— mobile phase A: to 900 mL of water R add 25 mL of a 60 g/L solution of acetic acid R and 6 mL of concentrated ammonia R1; adjust to pH 10.0 with dilute ammonia R2 or dilute acetic acid R and dilute to 1000.0 mL with water R;
— mobile phase B: acetonitrile R;
| Time (min) |
Mobile phase A (per cent V/V) |
Mobile phase B (per cent V/V) |
| 0 – 3 | 100 | 0 |
| 3 – 3.01 | 100 → 95 | 0 → 5 |
| 3.01 – 28 | 95 → 74 | 5 → 26 |
| 28 – 32 | 74 → 60 | 26 → 40 |
Flow rate: 1.0 mL/min.
Detection: Spectrophotometer at 254 nm.
Injection: 20 μL.
Identification of impurities: Use the chromatogram supplied with nicotine for system suitability CRS and the chromatogram obtained with reference solution (a) to identify the peaks due to impurities A, B, C, D, E, F and G.
Relative retention: With reference to nicotine (retention time = about 17.8 min): impurity E = about 0.3; impurity C = about 0.55; impurity F = about 0.7; impurity A = about 0.8; impurity D = about 0.86; impurity G = about 0.9; impurity B = about 1.6.
System suitability: Reference solution (a):
— resolution: minimum 2.5 between the peaks due to impurity G and nicotine.
Limits:
— impurities A, B, C, D, E, F, G: for each impurity, not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent);
— unspecified impurities: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.10 per cent);
— total: not more than 8 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.8 per cent);
— disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).
Water (2.5.12)
6.5 per cent to 8.0 per cent, determined on 0.100 g.
Sulfated ash (2.4.14)
Maximum 0.1 per cent, determined on 1.0 g.
ASSAY
Dissolve 0.180 g in 50 mL of anhydrous acetic acid R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20).
1 mL of 0.1 M perchloric acid is equivalent to 23.12 mg of C18H26N2O12.
STORAGE
Protected from light.
IMPURITIES
Specified impurities A, B, C, D, E, F, G.
A. (2S)-1,2,3,6-tetrahydro-2,3′-bipyridyl (anatabine),
B. 3-(1-methyl-1H-pyrrol-2-yl)pyridine (β-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),
F. 3-[(2S)-pyrrolidin-2-yl]pyridine (nornicotine),
G. 3-[(2S)-piperidin-2-yl]pyridine (anabasine).
