(Ph. Eur. 11.6 update)
Haloperidol Oral Drops
Action and use
Dopamine receptor antagonist; neuroleptic.
DEFINITION
Haloperidol Oral Solution is a solution of Haloperidol in a suitable vehicle.
The oral solution complies with the requirements stated under Oral Liquids and with the following requirements.
Content of haloperidol, C21H23ClFNO2
95.0 to 105.0% of the stated amount.
IDENTIFICATION
To a volume containing 20 mg of Haloperidol add 1 mL of 1M sodium hydroxide and extract with 10 mL of dichloromethane. Filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of haloperidol (RS 173).
TESTS
Acidity
pH, 2.5 to 3.5, Appendix V L.
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) Dilute a volume of the oral solution with sufficient solution A to produce a solution containing 0.01% w/v of Haloperidol.
(2) Dilute 1 volume of solution (1) to 200 volumes.
(3) 0.01% 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%).
ASSAY
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).
(1) Dilute a volume of the oral solution with sufficient solution A to produce a solution containing 0.005% w/v of Haloperidol.
(2) 0.005% w/v of haloperidol BPCRS.
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 20 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 content of C21H23ClFNO2 in the oral solution using the declared content of C21H23ClFNO2 in haloperidol BPCRS.
When Haloperidol Oral Solution or Haloperidol Oral Drops is prescribed or demanded and no strength is stated, an Oral Solution containing 0.2% w/v (2 mg/mL) of Haloperidol shall be dispensed or supplied.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Haloperidol.
