Pimozide Tablets

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.

test conditions
(a) Use Apparatus 2, rotating the paddle at 100 revolutions per minute.
(b) Use 900 mL of 0.01m hydrochloric acid, at a temperature of 37°, as the medium.
procedure

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) After 45 minutes withdraw a 20 mL sample of the medium and filter through a 0.45-µm polytetrafluoroethylene filter. Use the filtered medium, diluted with the dissolution medium if necessary, expected to contain 0.0002% w/v of Pimozide.
(2) 0.0002% w/v of pimozide BPCRS in water.
chromatographic conditions

The chromatographic conditions described under Related substances may be used.

determination of content

Calculate the total content of pimozide, C28H29F2N3O, in the medium from the chromatograms obtained and 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.

(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.
(2) Dilute 1 volume of solution (1) to 200 volumes with methanol.
(3) 0.005% w/v of pimozide BPCRS and 0.002% w/v of mebendazole in methanol.
chromatographic conditions
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (3 µm) (Hypersil ODS is suitable).
(b) Use linear gradient elution and the mobile phases described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 280 nm.
(f) Inject 10 µL of each solution.
mobile phase
Mobile phase A0.25% w/v of ammonium acetate and 0.85% w/v of tetrabutylammonium hydrogen sulfate.
Mobile phase Bacetonitrile.
system suitability

Equilibrate the column for at least 10 minutes with the initial mobile phase. 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.

limits

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%);

the sum of the areas of any secondary peaks is not greater than 1.5 times the principal peak in the chromatogram obtained with solution (2) (0.75%).

Uniformity of content

Tablets containing less than 2 mg and/or less than 2% w/w 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.

(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.
(2) 0.010% w/v of pimozide BPCRS in methanol.
(3) 0.005% w/v of pimozide BPCRS and 0.002% w/v of mebendazole in methanol.
chromatographic conditions

The chromatographic conditions described under Related substances may be used.

system suitability

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.

determination of content

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.

(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.
(2) 0.04% w/v of pimozide BPCRS in methanol.
(3) 0.004% w/v of pimozide BPCRS and 0.002% w/v of mebendazole BPCRS in methanol.
chromatographic conditions

The chromatographic conditions described under Related substances may be used.

system suitability

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.

determination of content

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.