Droperidol Tablets

Dopamine receptor antagonist; beta₁-adrenoceptor agonist; alpha-adrenoceptor agonist; neuroleptic.

Droperidol Tablets contain Droperidol.

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

95.0 to 105.0% of the stated amount.

A. Shake a quantity of the powdered tablets containing 20 mg of Droperidol with 10 mL of dichloromethane for 10 minutes, filter, evaporate the filtrate to dryness and dry the residue for 30 minutes at 90°. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of droperidol (RS 384).

B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the peak due to droperidol in the chromatogram obtained with solution (2).

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.

(a) Use Apparatus 2, rotating the paddle at 75 revolutions per minute.

(b) Use 900 mL of 0.1m hydrochloric acid, at a temperature of 37°, as the medium.

(1) Withdraw a sample of 10 mL of the medium, filter through a 15-µm membrane filter and immediately measure the absorbance of the filtered solution, diluted if necessary with the dissolution medium, at the maximum at 247 nm, Appendix II B, using dissolution medium in the reference cell.

(2) Measure the absorbance of a suitable solution of droperidol BPCRS using 0.1m hydrochloric acid in the reference cell.

Calculate the total content of droperidol, C₂₂H₂₂FN₃O₂, in the medium using the declared content of C₂₂H₂₂FN₃O₂ in droperidol BPCRS.

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

(1) Mix with the aid of ultrasound a quantity of the powdered tablets containing 0.1 g of Droperidol with 20 mL of dimethylformamide for 20 minutes, filter and dilute 5 volumes of the filtrate to 10 volumes with a 1% w/v solution of tetrabutylammonium hydrogen sulfate.

(2) Dilute 1 volume of solution (1) to 100 volumes with a mixture containing equal volumes of dimethylformamide and a 1% w/v solution of tetrabutylammonium hydrogen sulfate and further dilute 5 volumes of this solution to 20 volumes with the same solvent mixture.

(3) 0.0025% w/v each of droperidol BPCRS and benperidol EPCRS in a mixture containing equal volumes of dimethylformamide and a 1% w/v solution of tetrabutylammonium hydrogen sulfate.

(a) Use a stainless steel column (10 cm × 4.6 mm) packed with base-deactivated octadecylsilyl silica gel for chromatography (3 µm) (Hypersil C18 BDS 3µ is suitable).

(b) Use gradient elution and the mobile phases described below.

(c) Use a flow rate of 1.5 mL per minute.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 275 nm.

(f) Inject 20 µL of each solution.

(g) Inject 20 µL of a mixture of equal volumes of dimethylformamide and a 1% w/v solution of tetrabutylammonium hydrogen sulfate as a blank solution.

(h) Equilibrate the column with acetonitrile for at least 30 minutes before use and then equilibrate at the initial mobile phase composition for at least 30 minutes.

Mobile phase A  1% w/v solution of tetrabutylammonium hydrogen sulfate.

Mobile phase B  40 volumes of acetonitrile and 60 volumes of a 1% w/v solution of tetrabutylammonium hydrogen sulfate.

When the chromatogram is recorded under the prescribed conditions, the retention times for benperidol and droperidol are about 6.5 minutes and about 7 minutes respectively. The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor 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.

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) (0.25%);

the sum of the areas of any secondary peaks is not greater than four times the area of the principal peak in the chromatogram obtained with solution (2) (1%).

Disregard any peak obtained with the blank solution and any peak with an area less than 0.2 times the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).

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 Droperidol with 75 mL of methanol for 30 minutes, dilute to 100 mL with methanol, filter and dilute 10 mL of the resulting solution to 20 mL with water.

(2) 0.010% w/v of droperidol BPCRS in methanol (50%).

(3) 0.0025% w/v each of droperidol BPCRS and benperidol EPCRS in methanol (50%).

The chromatographic procedure described under Related substances may be used.

Inject solution (3). When the chromatogram is recorded under the prescribed conditions, the retention times for benperidol and droperidol are about 6.5 minutes and about 7 minutes respectively. The assay is not valid unless, in the chromatogram obtained with solution (3), the resolution factor 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.

Calculate the content of C₂₂H₂₂FN₃O₂ in the tablets using the declared content of C₂₂H₂₂FN₃O₂ in droperidol BPCRS.