Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Dopamine receptor antagonist; neuroleptic.
DEFINITION
Haloperidol Tablets contain Haloperidol.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of haloperidol, C21H23ClFNO2
95.0 to 105.0% of the stated amount.
IDENTIFICATION
To a quantity of the powdered tablets containing 10 mg of Haloperidol add 10 mL of water and 1 mL of 1M sodium hydroxide and extract with 10 mL of ether. Filter the ether extract through absorbent cotton, evaporate the filtrate to dryness and dry the residue at 60° at a pressure not exceeding 0.7 kPa. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of haloperidol (RS 173).
TESTS
Dissolution
Comply with the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 1, rotating the basket at 100 revolutions per minute.
(b) Use 900 mL of a solution containing of 0.2% w/v of sodium chloride and 8% v/v of 1M hydrochloric acid in water, at a temperature of 37°, as the medium.
PROCEDURE
(1) After 45 minutes withdraw a sample of the medium, filter and dilute with the dissolution medium if necessary, to produce a solution expected to contain 0.00017% w/v of Haloperidol.
(2) 0.00017% w/v of haloperidol BPCRS in dissolution medium.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 5 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 μm) (Hypersil ODS is suitable).
(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 247 nm.
(f) Inject 50 μL of each solution.
MOBILE PHASE
45 volumes of acetonitrile and 55 volumes of a 1% w/v solution of ammonium acetate.
DETERMINATION OF CONTENT
Calculate the total content of haloperidol, C21H23ClFNO2, in the medium from the chromatograms obtained and using the declared content of C21H23ClFNO2, in haloperidol BPCRS.
LIMITS
The amount of haloperidol released is not less than 70% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in a mixture of 1 volume of mobile phase A and 9 volumes of mobile phase B (solution A). Prepare the solutions immediately before use and protect from light.
(1) Shake a quantity of powdered tablets containing 10 mg of Haloperidol with 15 mL of solution A and mix with the aid of ultrasound. Dilute to 20 mL and filter.
(2) Dilute 1 volume of solution (1) to 200 volumes.
(3) 0.05% w/v of haloperidol for system suitability EPCRS.
(4) Dilute 1 volume of solution (2) to 5 volumes.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (10 cm × 4.6 mm) packed with base-deactivated end-capped octadecylsilyl silica gel for chromatography (3 μm) (Hypersil BDS is suitable).
(b) Use gradient elution and the mobile phase 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 230 nm.
(f) Inject 10 μL of each solution.
MOBILE PHASE
Mobile phase A 1.7% w/v of tetrabutylammonium hydrogen sulfate.
Mobile phase B acetonitrile.
| Time (Minutes) | Mobile phase A (% v/v) | Mobile phase B (% v/v) | Comment |
| 0-2 | 90 | 10 | isocratic |
| 2-17 | 90→50 | 10→50 | linear gradient |
| 17-22 | 50 | 50 | isocratic |
| 22-23 | 50→90 | 50→10 | linear gradient |
| 23-28 | 90 | 10 | re-equilibration |
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to haloperidol (retention time about 8 minutes) are: impurity B, about 0.9 and impurity D, about 1.6.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity B and haloperidol is at least 3.0.
LIMITS
Identify any peak corresponding to impurity B in the chromatogram obtained with solution (1), using the chromatogram obtained with solution (3), and multiply the area of this peak by a correction factor of 0.7.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity D is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the area of any peak corresponding to impurity B is not greater than 0.6 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%);
the area of any other secondary peak is not greater than 0.4 times the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of all secondary peaks is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (1.0%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.1%).
Uniformity of content
Tablets containing less than 2 mg and/or less than 2% w/w of Haloperidol 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) Place one tablet in 10 mL of the mobile phase, disperse with the aid of ultrasound for 2 minutes and centrifuge. If necessary, dilute the supernatant liquid with the mobile phase to produce a solution containing 0.005% w/v of Haloperidol.
(2) 0.005% w/v of haloperidol BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
The chromatographic procedure described under Dissolution may be used with an injection volume of 20 μL.
DETERMINATION OF CONTENT
Calculate the content of C21H23ClFNO2 in each tablet using the declared content of C21H23ClFNO2 in haloperidol BPCRS.
ASSAY
For tablets containing less than 2 mg and/or less than 2% w/w of Haloperidol
Use the average of the individual results determined in the test for Uniformity of content.
For tablets containing 2 mg or more and 2% w/w or more of Haloperidol
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Add 60 mL of the mobile phase to a quantity of the powdered tablets containing 20 mg of Haloperidol, disperse with the aid of ultrasound for 2 minutes, add sufficient mobile phase to produce 100 mL, mix and filter.
(2) 0.020% w/v of haloperidol BPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
The chromatographic procedure described under Dissolution may be used with an injection volume of 20 μL.
DETERMINATION OF CONTENT
Calculate the content of C21H23ClFNO2 in the tablets using the declared content of C21H23ClFNO2 in haloperidol BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Haloperidol.
