Quinine hydrochloride EUROPEAN PHARMACOPOEIA 6.

— signal-to-noise ratio : minimum 4 for the principal peak in C. R = C2H5, R′ = OCH3 : (S)-[(2R,4S,5R)-5-ethyl-1-
the chromatogram obtained with reference solution (d) ; azabicyclo[2.2.2]oct-2-yl](6-methoxyquinolin-4-
— mass distribution ratio : 3.5 to 4.5 for the peak due to yl)methanol (dihydroquinidine).
quinidine in the chromatogram obtained with reference
solution (b), tR′ being calculated from the peak due to 01/2008:0018
thiourea in the chromatogram obtained with reference corrected 6.0
solution (e) ; if necessary, adjust the concentration of
acetonitrile in the mobile phase.
QUININE HYDROCHLORIDE
Limits :
— impurity C : maximum 15 per cent ; Chinini hydrochloridum
— any impurity eluted before quinidine : for each impurity,
maximum 5 per cent ;
— any other impurity : for each impurity, maximum 2.5 per
cent ;
— disregard limit : the area of the principal peak in the
chromatogram obtained with reference solution (d)
(0.2 per cent).
Boron : maximum 5 ppm. Avoid where possible the use of
glassware.
Test solution. Dissolve 1.00 g in a mixture of 0.5 ml of C20H25ClN2O2,2H2O Mr 396.9
hydrochloric acid R and 4.0 ml of water R. [6119-47-7]
Reference solution. Dissolve 0.572 g of boric acid R in
DEFINITION
water R and dilute to 1000.0 ml with the same solvent.
Dilute 5.0 ml of the solution to 100.0 ml with water R. To Content : 99.0 per cent to 101.0 per cent of alkaloid
1.0 ml of this solution add 3.0 ml of water R and 0.5 ml of monohydrochlorides, expressed as (R)-[(2S,4S,5R)-5-ethenyl-
hydrochloric acid R. 1-azabicyclo[2.2.2]oct-2-yl](6-methoxyquinolin-4-yl)methanol
hydrochloride (dried substance).
Blank solution. Add 0.5 ml of hydrochloric acid R to 4.0 ml
of water R. CHARACTERS
Add 3.0 ml of a 100 g/l solution of 2-ethylhexane-1,3-diol R Appearance : white or almost white or colourless, fine, silky
in methylene chloride R to the test solution, to the reference needles, often in clusters.
solution and to the blank solution, then shake for 1 min. Solubility : soluble in water, freely soluble in ethanol (96 per
Allow to stand for 6 min. To 1.0 ml of the lower layer, add cent).
2.0 ml of a 3.75 g/l solution of curcumin R in anhydrous
acetic acid R and 0.3 ml of sulphuric acid R. Mix and after IDENTIFICATION
20 min add 25.0 ml of ethanol (96 per cent) R. Mix. The A. Thin-layer chromatography (2.2.27).
blank solution is yellow. Any red colour in the test solution
is not more intense than that in the reference solution. Test solution. Dissolve 0.10 g of the substance to be
examined in methanol R and dilute to 10 ml with the
Loss on drying (2.2.32) : 3.0 per cent to 5.0 per cent, same solvent.
determined on 1.000 g by drying in an oven at 130 °C. Reference solution. Dissolve 0.10 g of quinine
Sulphated ash (2.4.14) : maximum 0.1 per cent, determined sulphate CRS in methanol R and dilute to 10 ml with
on 1.0 g. the same solvent.
ASSAY Plate : TLC silica gel G plate R.
Dissolve 0.200 g in 20 ml of acetic anhydride R. Titrate with Mobile phase : diethylamine R, ether R, toluene R
0.1 M perchloric acid, using 0.15 ml of naphtholbenzein (10:24:40 V/V/V).
solution R as indicator. Application : 5 µl.
1 ml of 0.1 M perchloric acid is equivalent to 24.90 mg Development : twice over a path of 15 cm ; dry in a current
of C40H50N4O8S. of air for 15 min between the 2 developments.
Drying : at 105 °C for 30 min and allow to cool.
STORAGE
Detection : spray with iodoplatinate reagent R.
Protected from light.
Results : the principal spot in the chromatogram obtained
IMPURITIES with the test solution is similar in position, colour and
size to the principal spot in the chromatogram obtained
A. quinine,
with the reference solution.
B. Dissolve about 10 mg in water R and dilute to 10 ml with
the same solvent. To 5 ml of this solution add 0.2 ml of
bromine water R and 1 ml of dilute ammonia R2. A
green colour develops.
C. Dissolve 0.1 g in 3 ml of dilute sulphuric acid R and dilute
to 100 ml with water R. When examined in ultraviolet
light at 366 nm, an intense blue fluorescence appears
which disappears almost completely on the addition of
B. R = CH=CH2, R′ = H : (S)-[(2R,4S,5R)-5-ethenyl-1- 1 ml of hydrochloric acid R.
azabicyclo[2.2.2]oct-2-yl](quinolin-4-yl)methanol D. It gives the reactions of chlorides (2.3.1).
(cinchonine), E. pH (see Tests).

2800 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 6.0 Quinine hydrochloride

TESTS System suitability :

Solution S. Dissolve 1.0 g in carbon dioxide-free water R — resolution : minimum 3.0 between the peaks due to
prepared from distilled water R and dilute to 50 ml with the quinine and impurity A and minimum 2.0 between
same solvent. the peaks due to dihydroquinidine and quinine in the
Appearance of solution. Solution S is clear (2.2.1) and not chromatogram obtained with reference solution (c) ;
more intensely coloured than reference solution Y6 (2.2.2, — signal-to-noise ratio : minimum 4 for the principal peak in
Method II). the chromatogram obtained with reference solution (d) ;
pH (2.2.3) : 6.0 to 6.8. — mass distribution ratio : 3.5 to 4.5 for the peak due to
impurity A in the chromatogram obtained with reference
Dilute 10 ml of solution S to 20 ml with carbon dioxide-free solution (b), tR′ being calculated from the peak due to
water R. thiourea in the chromatogram obtained with reference
Specific optical rotation (2.2.7) : − 245 to − 258 (dried solution (e) ; if necessary, adjust the concentration of
substance). acetonitrile in the mobile phase.
Dissolve 0.500 g in 0.1 M hydrochloric acid and dilute to Limits :
25.0 ml with the same acid. — impurity C : maximum 10 per cent ;
Other cinchona alkaloids. Liquid chromatography (2.2.29) : — any impurity eluted before quinine : for each impurity,
use the normalisation procedure. maximum 5 per cent ;
Test solution. Dissolve 20 mg of the substance to be — any other impurity : for each impurity, maximum 2.5 per
examined in 5 ml of the mobile phase, with gentle heating if cent ;
necessary, and dilute to 10 ml with the mobile phase.
— disregard limit : the area of the principal peak in the
Reference solution (a). Dissolve 20 mg of quinine chromatogram obtained with reference solution (d)
sulphate CRS in 5 ml of the mobile phase, with gentle (0.2 per cent).
heating if necessary, and dilute to 10 ml with the mobile
phase. Sulphates (2.4.13) : maximum 500 ppm, determined on
solution S.
Reference solution (b). Dissolve 20 mg of quinidine
sulphate CRS (impurity A) in 5 ml of the mobile phase, with Barium. To 15 ml of solution S add 1 ml of dilute sulphuric
gentle heating if necessary, and dilute to 10 ml with the acid R. Allow to stand for 15 min. Any opalescence in the
mobile phase. solution is not more intense than that in a mixture of 15 ml
of solution S and 1 ml of distilled water R.
Reference solution (c). To 1 ml of reference solution (a) add
1 ml of reference solution (b). Loss on drying (2.2.32) : 6.0 per cent to 10.0 per cent,
determined on 1.000 g by drying in an oven at 105 °C.
Reference solution (d). Dilute 1.0 ml of reference solution (a)
to 10.0 ml with the mobile phase. Dilute 1.0 ml of this Sulphated ash (2.4.14) : maximum 0.1 per cent, determined
solution to 50.0 ml with the mobile phase. on 1.0 g.
Reference solution (e). Dissolve 10 mg of thiourea R in the ASSAY
mobile phase and dilute to 10 ml with the mobile phase.
Dissolve 0.250 g in 50 ml of ethanol (96 per cent) R and
Column : add 5.0 ml of 0.01 M hydrochloric acid. Titrate with
— size : l = 0.15-0.25 m, Ø = 4.6 mm ; 0.1 M sodium hydroxide, determining the end-point
potentiometrically (2.2.20). Read the volume added between
— stationary phase = octadecylsilyl silica gel for the 2 inflexion points.
chromatography R (5-10 µm).
1 ml of 0.1 M sodium hydroxide is equivalent to 36.09 mg
Mobile phase : dissolve 6.8 g of potassium dihydrogen of C20H25ClN2O2
phosphate R and 3.0 g of hexylamine R in 700 ml of water R,
adjust to pH 2.8 with dilute phosphoric acid R, add 60 ml of STORAGE
acetonitrile R and dilute to 1000 ml with water R.
Protected from light.
Flow rate : 1.5 ml/min.
Detection : spectrophotometer at 250 nm for reference IMPURITIES
solution (e) and at 316 nm for the other solutions.
A. quinidine,
Injection : 10 µl.
Run time : 2.5 times the retention time of quinine.
Identification of peaks : use the chromatogram obtained
with reference solution (a) to identify the peaks due to
quinine and impurity C ; use the chromatogram obtained
with reference solution (b) to identify the peaks due to
impurity A and dihydroquinidine ; the chromatogram
obtained with reference solution (c) shows 4 peaks due to
impurity A, quinine, dihydroquinidine and impurity C, which
are identified by comparison of their retention times with
those of the corresponding peaks in the chromatograms B. R = CH=CH2, R′ = H : (R)-[(2S,4S,5R)-5-ethenyl-1-
obtained with reference solutions (a) and (b). azabicyclo[2.2.2]oct-2-yl](quinolin-4-yl)methanol
(cinchonidine),
Relative retention with reference to quinine :
impurity C = about 1.4. C. R = C2H5, R′ = OCH3 : (R)-[(2S,4S,5R)-5-ethyl-1-
Relative retention with reference to impurity A : azabicyclo[2.2.2]oct-2-yl](6-methoxyquinolin-4-
dihydroquinidine = about 1.5. yl)methanol (dihydroquinine).

General Notices (1) apply to all monographs and other texts 2801