• British Pharmacopoeia Volume III
  • Formulated Preparations: Specific Monographs

Pimozide Tablets

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General Notices
Action and use

Dopamine receptor antagonist; neuroleptic.

Definition

Pimozide Tablets contain Pimozide.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of pimozide, C28H29F2N3O

95.0% to 105.0% of the stated amount.

Identification

A.  Shake a quantity of the powdered tablets containing 20  mg of Pimozide with 20  ml of dichloromethane for 5  minutes, filter through a glass microfibre filter (Whatman GF/C is suitable) and evaporate the filtrate to dryness under reduced pressure. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of pimozide (RS 389).

B.  In the Assay, the principal peak in the chromatogram obtained with solution (1) has the same retention time as the principal peak in the chromatogram obtained with solution (2).

Tests
Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using Apparatus 2. Use as the medium 900  ml of 0.01m hydrochloric acid and rotate the paddle at 100 revolutions per minute. Withdraw a sample of 20  ml of the medium and filter through a 0.45-µm polytetrafluoroethylene filter. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) dilute the solution from the sample, if necessary, with the dissolution medium to give a solution containing 0.0002% w/v of Pimozide. Solution (2) contains 0.0002% w/v of pimozide BPCRS.

The chromatographic procedure described under Related substances may be used.

Calculate the total content of pimozide, C28H29F2N3O, in the medium using the declared content of C28H29F2N3O in pimozide BPCRS.

Related substances

Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) add 20  ml of methanol to a quantity of the powdered tablets containing 40  mg of Pimozide, shake for 30  minutes, mix with the aid of ultrasound for 10  minutes, centrifuge and filter the supernatant liquid through a 0.45-µm polytetrafluoro-ethylene filter. For solution (2) dilute 1  volume of solution (1) to 200  volumes with methanol. Solution (3) contains 0.005% w/v of pimozide BPCRS and 0.002% w/v of mebendazole in methanol.

The chromatographic procedure may be carried out using (a) a stainless steel column (10  cm × 4.6  mm) packed with end-capped octadecylsilyl silica gel for chromatography (3 µm) (Hypersil ODS is suitable). Carry out a linear gradient elution with a flow rate of 2  ml per minute using the following conditions.

Mobile phase A  A solution containing 0.25% w/v of ammonium acetate and 0.85% w/v of tetrabutylammonium hydrogen sulphate.

Mobile phase B  Acetonitrile.

bp2010_v3_02_09_formulated_preparations_specific_monographs pimozide_tablets-1.png


Use a detection wavelength of 280  nm. Equilibrate the column for at least 10  minutes with the initial mobile phase.

Inject 10 µl of each solution. The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 5.0. In the chromatogram obtained with solution (1) the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%) and the sum of the areas of any secondary peaks is not greater than 1.5  times the area of the principal peak in the chromatogram obtained with solution (2) (0.75%).

Tablets containing 2  mg or less of Pimozide 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. For solution (1) shake one tablet with 7  ml of methanol for 30  minutes, dilute with sufficient methanol to produce a solution containing 0.01% w/v of Pimozide, mix with the aid of ultrasound for 10  minutes, centrifuge and filter the supernatant liquid through a 0.45-µm polytetrafluoroethylene filter. Solution (2) contains 0.010% w/v of pimozide BPCRS in methanol. Solution (3) contains 0.005% w/v of pimozide BPCRS and 0.002% w/v of mebendazole in methanol.

The chromatographic procedure described under Related substances may be used.

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 5.0.

Calculate the content of C28H29F2N3O in each tablet using the declared content of C28H29F2N3O in pimozide BPCRS.

Assay

Weigh and powder 20  tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) shake a quantity of the powdered tablets containing 20  mg of Pimozide with 35  ml of methanol for 30  minutes, dilute to 50  ml with methanol, mix with the aid of ultrasound for 10  minutes, centrifuge and filter the supernatant liquid through a 0.45-µm polytetrafluoroethylene filter. Solution (2) contains 0.04% w/v of pimozide BPCRS in methanol. Solution (3) contains 0.004% w/v of pimozide BPCRS and 0.002% w/v of mebendazole EPCRS in methanol.

The chromatographic procedure described under Related substances may be used.

Inject 10 µl of each solution. The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 5.0.

Calculate the content of C28H29F2N3O in the tablets using the declared content of C28H29F2N3O in pimozide BPCRS.

Storage

Pimozide Tablets should be kept protected from light.

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