FLURBIPROFEN Flurbiprofenum

Flurbiprofen EUROPEAN PHARMACOPOEIA 5.0
A. Melting point (2.2.14) : 114 °C to 117 °C.
B. Dissolve 0.10 g in 0.1 M sodium hydroxide and dilute to
100.0 ml with the same alkaline solution. Dilute 1.0 ml of
the solution to 100.0 ml with 0.1 M sodium hydroxide.
Examined between 230 nm and 350 nm (2.2.25), the
solution shows an absorption maximum at 247 nm. The
specific absorbance at the maximum is 780 to 820.
C. Examine by infrared absorption spectrophotometry
(2.2.24), comparing with the spectrum obtained with
flurbiprofenCRS. 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 add 1.0 ml of the filtrate. Mix, allow to
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.
TESTS
Appearance of solution. Dissolve1.0ginmethanol R and
dilute to 10 ml with the same solvent. The solution is clear
(2.2.1) and colourless (2.2.2, Method I).
Optical rotation (2.2.7). Dissolve 0.50 g in methanol R and
dilute to 20.0 ml with the same solvent. The angle of optical
rotation is −0.1° to + 0.1°.
Related substances. Examine by liquid chromatography
(2.2.29).
Test solution. Dissolve 0.20 g of the substance to be
examined in a mixture of 45 volumes of acetonitrile R and
55 volumes of water R and dilute to 100.0 ml with the same
mixture of solvents.
Reference solution (a). Dilute 1.0 ml of the test solution
to50.0mlwithamixtureof45volumesofacetonitrile R
and 55 volumes of water R. Dilute1.0mlofthesolutionto
10.0 ml with a mixture of 45 volumes of acetonitrile R and
55 volumes of water R.
Reference solution (b). Dissolve 10.0 mg of flurbiprofen
impurity A CRS in a mixture of 45 volumes of acetonitrile R
and 55 volumes of water R and dilute to100.0 ml with the
same mixture of solvents. Dilute 10.0 ml of this solution to
100.0mlwithamixtureof45volumesofacetonitrile R and
55 volumes of water R.
Reference solution (c). Dissolve 10 mg of the substance to
be examined in a mixture of 45 volumes of acetonitrile R
and 55 volumes of water R and dilute to 100.0 ml with the
same mixture of solvents. Dilute 1.0 ml of the solution to
10.0 ml with reference solution (b).
The chromatographic procedure may be carried out using:
— a stainless steel column 0.15 m long and 3.9 mm in
internal diameter packed with octadecylsilyl silica gel for
chromatography R (5 µm),
— as mobile phase at a flow rate of 1 ml/min a mixture
of 5 volumes of glacial acetic acid R, 35 volumes of
acetonitrile R and 60 volumes of water R,
— as detector a spectrophotometer set at 254 nm.
Inject 10 µl of reference solution (c). Adjust the sensitivity
of the system so that the heights of the two principal peaks
in the chromatogram obtained are at least 40 per cent of
the full scale of the recorder. The test is not valid unless the
resolution between the peak corresponding to impurity A
and the peak corresponding to flurbiprofen is at least 1.5.
Inject 10 µl of the test solution and of reference solutions (a)
and (b). Continue the chromatography for twice the retention
time of flurbiprofen. In the chromatogram obtained with
the test solution the area of any peak corresponding to
impurity A is not greater than the area of the peak in the
chromatogram obtained with reference solution (b) (0.5 per
cent); the area of any peak, apart from the principal peak
and the peak due to impurity A, is not greater than the area
of the principal peak in the chromatogram obtained with
reference solution (a) (0.2 per cent) and the sum of the areas
of any such peaks is not greater than five times the area
of the principal peak in the chromatogram obtained with
reference solution (a) (1.0 per cent). Disregard any peak with
an area less than 0.1 times that of the principal peak in the
chromatogram obtained with reference solution (a) (0.02 per
cent).
Heavy metals (2.4.8). Dissolve 2.0 g in a mixture of
10 volumes of water R and 90 volumes of methanol R and
dilute to 20 ml with the same mixture of solvents. 12 ml
of the solution complies with limit test B for heavy metals
(10 ppm). Prepare the standard using lead standard solution
(1 ppm Pb) obtained by diluting lead standard solution
(100 ppm Pb) R with a mixture of 10 volumes of water R and
90 volumes of methanol R.
Loss on drying (2.2.32). Not more than 0.5 per cent,
determined on 1.000 g by drying at 60 °C at a pressure not
exceeding 0.7 kPa for 3 h.
Sulphated ash (2.4.14). Not more than 0.1 per cent,
determined on 1.0 g in a platinum crucible.
ASSAY
Dissolve 0.200 g in 50 ml of alcohol R. Titratewith
0.1 M sodium hydroxide, determining the end-point
potentiometrically (2.2.20).
1mlof0.1 M sodium hydroxide is equivalent to 24.43 mg
of C 15H 13FO 2.
IMPURITIES
A. R = R′ =H:(2RS)-2-(biphenyl-4-yl)propanoic acid,
B. R = CH(CH 3)-CO 2H: 2-(2-fluorobiphenyl-4-yl)-2,3dimethylbutanedioic
acid,
C. C. R = OH, R′ =F:(2RS)-2-(2-fluorobiphenyl-4-yl)-2hydroxypropanoic
acid,
D. R = CO-CH 3:1-(2-fluorobiphenyl-4-yl)ethanone,
E. R = CO 2H: 2-fluorobiphenyl-4-carboxylic acid.
1624 See the information section on general monographs (cover pages)