(Pentoxyverine Hydrogen Citrate, Ph. Eur. monograph 1621)
C26H39NO10 525.6 23142-01-0
Action and use
Cough suppressant.
DEFINITION
2-[2-(Diethylamino)ethoxy]ethyl 1-phenylcyclopentanecarboxylate dihydrogen 2-hydroxypropane-1,2,3-tricarboxylate.
Content
98.5 per cent to 101.0 per cent (dried substance).
CHARACTERS
Appearance
White or almost white, crystalline powder.
Solubility
Freely soluble in water, very soluble in glacial acetic acid, freely soluble in methanol, soluble in ethanol (96 per cent) and in methylene chloride.
mp
About 93 °C.
IDENTIFICATION
A. Infrared absorption spectrophotometry (2.2.24).
Comparison: Ph. Eur. reference spectrum of pentoxyverine hydrogen citrate.
B. Dissolve 0.25 g in 5 mL of water R. The solution gives the reaction of citrates (2.3.1).
TESTS
Solution S
Dissolve 5.0 g in carbon dioxide-free water R and dilute to 50 mL with the same solvent.
Appearance of solution
Solution S is clear (2.2.1) and not more intensely coloured than reference solution Y6 (2.2.2, Method II).
pH (2.2.3)
3.3 to 3.7 for solution S.
Related substances
Liquid chromatography (2.2.29).
Test solution: Dissolve 25.0 mg of the substance to be examined in the mobile phase and dilute to 25.0 mL with the mobile phase.
Reference solution: Introduce 5.0 mg of pentoxyverine impurity A CRS and 5.0 mg of pentoxyverine impurity B CRS in a conical flask, add 5.0 mL of the test solution and dilute to 100.0 mL with the mobile phase.
Dilute 3.0 mL of the solution to 50.0 mL with the mobile phase.
Column:
— size: l = 0.15 m, Ø = 3.9 mm,
— stationary phase: end-capped octylsilyl silica gel for chromatography R (5 μm) with a pore size of 10 nm and a carbon loading of 12 per cent,
— temperature: 50 °C.
Mobile phase: Mix 35 volumes of acetonitrile R and 65 volumes of a 1.5 g/L solution of sodium heptanesulfonate R adjusted to pH 3.0 with dilute sulfuric acid R.
Flow rate: 1.0 mL/min.
Detection: Spectrophotometer at 205 nm.
Injection: 20 μL.
Run time: 3 times the retention time of pentoxyverine.
Relative retention: With reference to pentoxyverine (retention time = about 6 min): impurity B = about 0.8; impurity A = about 1.5.
System suitability: Reference solution:
— resolution: minimum of 5.0 between the peaks due to pentoxyverine and to impurity A,
— signal-to-noise ratio: minimum of 100 for the peak due to pentoxyverine,
— symmetry factor: maximum of 2.0 for the peak due to pentoxyverine.
Limits:
— impurity A: not more than the area of the corresponding peak in the chromatogram obtained with the reference solution (0.3 per cent),
— impurity B: not more than the area of the corresponding peak in the chromatogram obtained with the reference solution (0.3 per cent),
— any other impurity: not more than one-third of the area of the peak due to pentoxyverine in the chromatogram obtained with the reference solution (0.1 per cent),
— total of any other impurity: not more than the area of the peak due to pentoxyverine in the chromatogram obtained with the reference solution (0.3 per cent),
— disregard limit: 0.1 times the area of the peak due to pentoxyverine in the chromatogram obtained with the reference solution (0.03 per cent); disregard any peak with a retention time less than or equal to 2.5 min.
Loss on drying (2.2.32)
Maximum 0.5 per cent, determined on 1.000 g by drying in vacuo at 60 °C for 4 h.
Sulfated ash (2.4.14)
Maximum 0.1 per cent, determined on 1.0 g.
ASSAY
Dissolve 0.400 g in 70 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 52.56 mg of C26H39NO10.
STORAGE
Protected from light.
IMPURITIES
A. 1-phenylcyclopentanecarboxylic acid,
B. 2-(diethylamino)ethyl 1-phenylcyclopentanecarboxylate (caramiphen).
