DROPERIDOL Droperidolum

EUROPEAN PHARMACOPOEIA 5.0 Droperidol
B.R1=CH3,R2=H:(1RS)-1-phenyl-1-(pyridin-2-yl)ethanol, C. R1=H,R2=CH2-CH2-N(CH3) 2: N,N-dimethyl-2-[(RS)-1phenyl(pyridin-2-yl)methoxy]ethanamine,
D. phenyl(pyridin-2-yl)methanone (2-benzoylpyridine).
DROPERIDOL
Droperidolum
01/2005:1010
Reference solution (a). Dissolve 30 mg of droperidol CRS
in a mixture of 1 volume of acetone R and 9 volumes of
methanol R and dilute to 10 ml with the same mixture
of solvents.
Reference solution (b). Dissolve 30 mg of droperidol CRS
and 30 mg of benperidol CRS in a mixture of 1 volume
of acetone R and 9 volumes of methanol R and dilute to
10mlwiththesamemixtureofsolvents.
Apply to the plate 10 µl of each solution. Develop over a
path of 15 cm using a mixture of 1 volume of acetone R
and 9 volumes of methanol R. Allow the plate to dry in air
and examine in ultraviolet light at 254 nm. The principal
spot in the chromatogram obtained with the test solution
is similar in position and size to the principal spot in the
chromatogram obtained with reference solution (a). The
test is not valid unless the chromatogram obtained with
reference solution (b) shows 2 clearly separated spots.
C. Dissolve about 10 mg in 5 ml of ethanol R. Add0.5mlof
dinitrobenzene solution R and 0.5 ml of 2Malcoholic
potassium hydroxide R. Avioletcolourisproducedand
becomes brownish-red after 20 min.
D.Mixabout5mgwith45mgofheavy magnesium oxide R
and ignite in a crucible until an almost white residue is
obtained (usually less than 5 min). Allow to cool, add 1 ml
of water R, 0.05mlofphenolphthalein solution R1 and
about 1 ml of dilute hydrochloric acid R to render the
solution colourless. Filter. To a freshly prepared mixture
of 0.1 ml of alizarin S solution R and 0.1 ml of zirconyl
nitrate solution R, add1.0mlofthefiltrate.Mix,allowto
stand for 5 min and compare the colour of the solution
with that of a blank prepared in the same manner. The
test solution is yellow and the blank is red.
C22H22FN3O2 Mr 379.4
TESTS
Appearance of solution. Dissolve 0.20 g in methylene
chloride R and dilute to 20.0 ml with the same solvent. The
solution is clear (2.2.1) and not more intensely coloured
DEFINITION
than reference solution BY5 (2.2.2, Method II).
Droperidol contains not less than 99.0 per cent and
not more than the equivalent of 101.0 per cent of
1-[1-[4-(4-fluorophenyl)-4-oxobutyl]-1,2,3,6-tetrahydropyridin-
4-yl]-1,3-dihydro-2H-benzimidazol-2-one, calculated with
reference to the dried substance.
Related substances. Examinebyliquidchromatography
(2.2.29). Prepare the solutions immediately before use.
Test solution. Dissolve0.10gofthesubstancetobe
examined in dimethylformamide R and dilute to 10.0 ml
with the same solvent.
CHARACTERS
Reference solution (a). Dissolve 2.5 mg of droperidol CRS
A white or almost white powder, practically insoluble in
water, freely soluble in dimethylformamide and in methylene
and 2.5 mg of benperidol CRS in dimethylformamide R and
dilute to 100.0 ml with the same solvent.
chloride, sparingly soluble in alcohol.
Reference solution (b). Dilute 1.0 ml of the test solution to
It shows polymorphism.
100.0 ml with dimethylformamide R. Dilute 5.0 ml of this
IDENTIFICATION
First identification: A.
Second identification: B, C, D.
A. Examine by infrared absorption spectrophotometry
(2.2.24), comparing with the spectrum obtained with
droperidol CRS. Examine the substances prepared as
discs. If the spectra obtained show differences, dissolve
solution to 20.0 ml with dimethylformamide R.
The chromatographic procedure may be carried out using:
— a stainless steel column 0.10 m long and 4.6 mm
in internal diameter packed with base-deactivated
octadecylsilyl silica gel for chromatography R (3 µm),
— as mobile phase at a flow rate of 1.5 ml/min:
mobile phase A: acetonitrile R,
the substance to be examined and the reference substance mobile phase B: 10g/lsolutionoftetrabutylammonium
separately in the minimum volume of acetone R,
hydrogen sulphate R1,
evaporate to dryness on a water-bath and record new
spectra using the residues.
B. Examine by thin-layer chromatography (2.2.27), using
silica gel GF254 R as the coating substance.
Time
(min)
0-15
Mobile phase A
(per cent V/V)
0 → 40
Mobile phase B
(per cent V/V)
100 → 60
Test solution. Dissolve 30 mg of the substance to be
15 - 20 40 60
examined in a mixture of 1 volume of acetone R and
9 volumes of methanol R and dilute to 10 ml with the
20 - 25 40 → 0 60 → 100
same mixture of solvents.
— as detector a spectrophotometer set at 275 nm.
GeneralNotices(1)applytoallmonographsandothertexts 1487

Droperidol EUROPEAN PHARMACOPOEIA 5.0
Adjust the sensitivity of the system so that the height of the
principal peak in the chromatogram obtained with 10 µl of
reference solution (b) is at least 50 per cent of the full scale
of the recorder.
Inject10µlofreferencesolution(a). Whenthechromatogram
is recorded in the prescribed conditions, the retention times
are: benperidol about 6.5 min and droperidol about 7 min.
The test is not valid unless the resolution between the peaks
due to droperidol and benperidol is at least 2.0. If necessary,
adjust the final concentration of acetonitrile in the mobile
phase or adjust the time programme for the linear gradient.
Inject 10 µl of dimethylformamide R as a blank, 10 µl of
thetestsolutionand10µlofreferencesolution(b).Inthe
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) (0.25 per cent); the
sumoftheareasofallthepeaks,apartfromtheprincipal
peak,isnotgreaterthantwicetheareaoftheprincipalpeak
in the chromatogram obtained with reference solution (b)
(0.5 per cent). Disregard any peak obtained with the blank
and any peak with an area less than 0.2 times the area of the
principal peak in the chromatogram obtained with reference
solution (b).
Heavy metals (2.4.8). 1.0 g complies with limit test D for
heavy metals (20 ppm). Prepare the standard using 2 ml of
lead standard solution (10 ppm Pb) R.
Loss on drying (2.2.32). Not more than 0.5 per cent,
determined on 1.000 g by drying in an oven at 100-105 °C.
Sulphated ash (2.4.14). Not more than 0.1 per cent,
determined on 1.0 g.
ASSAY
Dissolve0.300gin50mlofamixtureof1volumeof
anhydrous acetic acid R and 7 volumes of methyl ethyl
ketone R. Using0.2mlofnaphtholbenzein solution R,
titrate with 0.1 M perchloric acid until the colour changes
from orange-yellow to green.
1mlof0.1Mperchloric acid is equivalent to 37.94 mg of
C22H22FN3O2. STORAGE
Store protected from light.
IMPURITIES
A. 1-(1,2,3,6-tetrahydropyridin-4-yl)-1,3-dihydro-2Hbenzimidazol-2-one,
B. 1-[1-[4-(2-fluorophenyl)-4-oxobutyl]-1,2,3,6tetrahydropyridin-4-yl]-1,3-dihydro-2H-benzimidazol-2one,
C. 1-[4-(4-fluorophenyl)-4-oxobutyl]-4-(2-oxo-2,3-dihydro-1Hbenzimidazol-1-yl)pyridinium
chloride,
D. (1RS)-1-[4-(4-fluorophenyl)-4-oxobutyl]-4-(2-oxo-2,3dihydro-1H-benzimidazol-1-yl)-1,2,3,6-tetrahydropyridine
1-oxide,
E. 1-[1-[4-[4-[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-3,
6-dihydropyridin-1(2H)-yl]-1-oxobutyl]phenyl]-1,2,3,6tetrahydropyridin-4-yl]-1,3-dihydro-2H-benzimidazol-2one.
1488 See the information section on general monographs (cover pages)