Promethazine Oral Solution
Action and use
Histamine H1 receptor antagonist; antihistamine.
Definition
Promethazine Oral Solution is a solution containing Promethazine Hydrochloride in a suitable flavoured vehicle.
Content of promethazine hydrochloride, C17H20N2S,HCl
90.0 to 110.0% of the stated amount.
Identification
Carry out the method for identification of phenothiazines, Appendix III A, but applying as solution (1) 5 µL of a solution prepared by diluting a suitable volume of the oral solution with water to contain 0.08% w/v of Promethazine Hydrochloride.
Related substances
Carry out the method for thin-layer chromatography, Appendix III A, protected from light under an atmosphere of nitrogen using silica gel GF254 as the coating substance (Merck silica gel 60 F254 plates are suitable) and a mixture of 15 volumes of diethylamine, 45 volumes of hexane and 50 volumes of acetone as the mobile phase but allowing the solvent front to ascend 12 cm above the line of application. Apply separately to the plate 10 µL of each of the following freshly prepared solutions. For solution (1) add 50 mL of water and 10 mL of a 5% w/v solution of sodium hydroxide to a quantity of the oral solution containing 20 mg of Promethazine Hydrochloride in a separating funnel and swirl to mix. Extract with two 100 mL quantities of chloroform, shaking vigorously for 1 minute each time, and filter successively through anhydrous sodium sulfate, washing the sodium sulfate with 50 mL of chloroform. Evaporate the combined extracts and washings to dryness at 30° using a rotary evaporator and dissolve the residue in 2 mL of a mixture of 5 volumes of diethylamine and 95 volumes of methanol. For solution (2) dilute 1 volume of solution (1) to 200 volumes with the same solvent. Solution (3) contains 0.01% w/v of isopromethazine hydrochloride BPCRS in the same solvent. Solution (4) contains 0.025% w/v of promethazine sulfoxide BPCRS in the same solvent. After removal of the plate, allow it to dry in air, spray with a 20% w/v solution of perchloric acid and heat at 100° for 5 minutes. In the chromatogram obtained with solution (1) any spot corresponding to isopromethazine is not more intense than the principal spot in the chromatogram obtained with solution (3) (1%), any spot corresponding to promethazine sulfoxide is not more intense than the principal spot in the chromatogram obtained with solution (4) (2.5%) and any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%). Disregard any spot remaining on the line of application.
Assay
Carry out the following procedure protected from light. To a weighed quantity containing 10 mg of Promethazine Hydrochloride add 25 mL of water and 5 mL of a 5% w/v solution of sodium hydroxide. Extract the mixture with two 50 mL quantities of chloroform, shaking vigorously for 1 minute each time, evaporate the combined extracts to dryness at about 30° at a pressure of 2 kPa and dissolve the residue in sufficient 0.1m hydrochloric acid to produce 50 mL (solution A). Dilute 10 mL of solution A to 50 mL with water (solution B). To a further 10 mL of solution A add 5 mL of peroxyacetic acid solution, allow to stand for 10 minutes and add sufficient water to produce 50 mL (solution C). Measure the absorbance of solution C at the maximum at 336 nm, Appendix II B, using solution B in the reference cell and measure the absorbance of solution B at the same wavelength using water in the reference cell. Repeat the procedure using a 0.02% w/v solution of promethazine hydrochloride BPCRS in 0.1m hydrochloric acid in place of solution A and beginning at the words ‘Dilute 10 mL of...’. Determine the weight per mL of the oral solution, Appendix V G, and calculate the content of C17H20N2S,HCl, weight in volume, using the declared content of C17H20N2S,HCl in promethazine hydrochloride BPCRS. The result is not valid if the absorbance of solution B is more than 0.10.
Storage
Promethazine Oral Solution should be protected from light.