Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Vasodilator.
DEFINITION
Ethyl (13aS,13bS)-13a-ethyl-2,3,5,6,13a,13b-hexahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12- carboxylate.
Content
98.5 per cent to 101.5 per cent (dried substance).
CHARACTERS
Appearance
White or slightly yellow, crystalline powder.
Solubility
Practically insoluble in water, soluble in methylene chloride, slightly soluble in anhydrous ethanol.
IDENTIFICATION
A. Specific optical rotation (see Tests).
B. Infrared absorption spectrophotometry (2.2.24).
Comparison vinpocetine CRS.
TESTS
Specific optical rotation (2.2.7)
+ 127 to + 134 (dried substance).
Dissolve 0.25 g in dimethylformamide R and dilute to 25.0 mL with the same solvent.
Related substances
Liquid chromatography (2.2.29).
Test solution Dissolve 50.0 mg of the substance to be examined in the mobile phase and dilute to 50.0 mL with the mobile phase.
Reference solution (a) Dilute 1.0 mL of the test solution to 50.0 mL with the mobile phase.
Reference solution (b) Dissolve 5.0 mg of vinpocetine impurity B CRS, 6.0 mg of vinpocetine impurity A CRS, 5.0 mg of vinpocetine impurity C CRS and 5.0 mg of vinpocetine impurity D CRS in the mobile phase and dilute to 50.0 mL with the mobile phase.
Reference solution (c) Dilute 1.0 mL of reference solution (a) and 1.0 mL of reference solution (b) to 20.0 mL with the mobile phase.
Column:
— size: l = 0.25 m, Ø = 4.6 mm;
— stationary phase: end-capped octadecylsilyl silica gel for chromatography R (5 µm).
Mobile phase 15.4 g/L solution of ammonium acetate R, acetonitrile R (45:55 V/V). Flow rate 1.0 mL/min.
Detection Spectrophotometer at 280 nm.
Injection 15 µL.
Run time 3 times the retention time of vinpocetine.
Relative retention With reference to vinpocetine (retention time = about 16 min): impurity A = about 0.4; impurity D = about 0.68; impurity B = about 0.75; impurity C = about 0.83.
System suitability Reference solution (c):
— resolution: minimum 2.0 between the peaks due to impurities D and B.
Limits:
— impurity A: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (c) (0.6 per cent);
— impurities B, D: for each impurity, not more than the area of the corresponding peak in the chromatogram obtained with reference solution (c) (0.5 per cent);
— impurity C: not more than 0.6 times the area of the corresponding peak in the chromatogram obtained with reference solution (c) (0.3 per cent);
— unspecified impurities: for each impurity, not more than the area of the peak due to vinpocetine in the chromatogram obtained with reference solution (c) (0.10 per cent);
— total: not more than 10 times the area of the peak due to vinpocetine in the chromatogram obtained with reference solution (c) (1.0 per cent);
— disregard limit: 0.5 times the area of the peak due to vinpocetine in the chromatogram obtained with reference solution (c) (0.05 per cent).
Loss on drying (2.2.32)
Maximum 0.5 per cent, determined on 1.000 g by drying in vacuo in an oven at 100 °C for 3 h.
Sulfated ash (2.4.14)
Maximum 0.1 per cent, determined on 1.0 g.
ASSAY
Dissolve 0.300 g in 50 mL of a mixture of equal volumes of acetic anhydride R and 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 35.05 mg of C22H26N2O2.
IMPURITIES
Specified impurities A, B, C, D.
A. ethyl (12S,13aS,13bS)-13a-ethyl-12-hydroxy-2,3,5,6,12,13,13a,13b-octahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12-carboxylate (ethyl vincaminate),
B. methyl (13aS,13bS)-13a-ethyl-2,3,5,6,13a,13b-hexahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12- carboxylate (apovincamine),
C. ethyl (13aS,13bS)-13a-ethyl-10-methoxy-2,3,5,6,13a,13b-hexahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12-carboxylate (methoxyvinpocetine),
D. ethyl (12RS,13aRS,13bRS)-13a-ethyl-2,3,5,6,12,13,13a,13b-octahydro-1H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12-carboxylate (dihydrovinpocetine).
