Action and use
Serotonin (5HT) receptor partial agonist; prophylaxis of migraine.
Definition
Pizotifen Tablets contain Pizotifen Malate.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of pizotifen, C19H21NS
90.0 to 110.0% of the stated amount.
Identification
A. To a quantity of the powdered tablets containing the equivalent of 10 mg of pizotifen add 50 mL of
water, mix with the aid of ultrasound for 15 minutes and centrifuge. Make the clear supernatant liquid alkaline with 5
m sodium hydroxide and extract with three 25 mL quantities of
ether, washing each extract with the same 20 mL of
water. Combine the ether extracts, dry with
anhydrous sodium sulfate, filter and evaporate the filtrate to dryness. The
infrared absorption spectrum of the residue,
Appendix II A, is concordant with the
reference spectrum of pizotifen (
RS 276).
B. In the test for Related substances, the principal spot in the chromatogram obtained with solution (1) corresponds to the spot in the chromatogram obtained with solution (2).
C. In the test for Uniformity of content, the chromatogram obtained with solution (1) shows a peak with the same retention time as the peak due to pizotifen in the chromatogram obtained with solution (2).
Tests
Related substances
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in a mixture of 3 volumes of 13.5m ammonia, 100 volumes of chloroform and 200 volumes of methanol (solvent A).
(1) Mix a quantity of the powdered tablets containing the equivalent of 6 mg of pizotifen with 60 mL of solvent A for 20 minutes, centrifuge, evaporate 50 mL of the clear supernatant liquid to dryness at 40° at a pressure of 2 kPa and dissolve the residue in 2 mL of solvent A. Centrifuge and use the supernatant liquid.
(3) Dilute 1 volume of solution (1) to 100 volumes with solvent A.
(4) Dilute 1 volume of solution (3) to 2 volumes with solvent A.
chromatographic conditions
(a) Use as the coating
silica gel (Merck silica gel 60 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 20 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in a current of warm air for 5 minutes, spray with a mixture of 1 volume of
potassium iodobismuthate solution and 10 volumes of 2
m acetic acid and then with
hydrogen peroxide solution (
10 vol), cover immediately with a glass plate and examine in daylight.
mobile phase
1 volume of 13.5m ammonia, 15 volumes of absolute ethanol and 85 volumes of toluene.
limits
Any secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (3) (1%) and not more than two such spots are more intense than the spot in the chromatogram obtained with solution (4) (0.5%). Disregard any spots with Rf values lower than 0.1.
Uniformity of content
Tablets containing less than 2 mg and/or less than 2% w/w of pizotifen comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Add sufficient mobile phase to one tablet to produce a solution containing the equivalent of 0.0050% w/v of pizotifen, mix with the aid of ultrasound until the tablet has disintegrated, stir for 15 minutes and centrifuge.
chromatographic conditions
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 256 nm.
(f) Inject 20 µL of each solution.
mobile phase
0.3 volume of triethylamine, 45 volumes of water and 55 volumes of acetonitrile.
determination of content
Calculate the content of C19H21NS in each tablet using the declared content of C19H21NS in pizotifen malate BPCRS.
Assay
Calculate the content of C19H21NS using the average of the individual results determined in the test for Uniformity of content.
Storage
Pizotifen Tablets should be protected from light.
Labelling
The quantity of active ingredient is stated in terms of the equivalent amount of pizotifen.