.AMANTADlNE HYDROCHLORIDEAmantadine Hydrochloride

to produce 50 ml (solution A). The solution gives reaction A of aluminium salts, Appendix 3.1. B: Solution A gives reaction A of sulphates. Appendix 3.1: pH Between 2.5 and 4.0, determined in a 2% w/v solution. Appendix 8.11. Clarity and colour of solution: Solution A is not more opalescent than opalescence standard OS3, Appendix 6.1, and is colourless. Appends 6.2. Alkalis and alkaline-earth metals: To 20 ml of solution A add 100 ml of water, heat and add 0.1 ml of methyl red solution. Add 6M ammonia until the colour changes to yellow, dilute to 150 ml with water, heat to boiling'and fiter. Evaporate 75 ml of the filtrate to dryness on a water-bath and ignite. The weight of the residue does not exceed 2 mg (0.4%). Ammonium salts: Heat 1 g with 10 ml of sodium hydroxide solution on a water-bath for 1 minute, the odour of ammonia is not perceptible. Arsenic: Dissolve 3.3 g in 50 ml of water and add 10 ml of stannated hydrochloric acid. The resulting solution complies with the limit test for arsenic. Appendix 3.9 (3 ppm). Heavy metals: Not more than 40 ppm, determined by Method A on 0.5 g dissolved in 1 ml of dilute acetic acid and sufficient water to produce 25ml, Appendix 3.12.Iron: 8 ml of solution A diluted to 10 ml complies with the limit test for iron, Appendix 3.13, but using 0.3 ml in place of 0.1 ml of thioglycollic acid (100 ppm). Assay: Weigh accurately about 0.6 g and dissolve in 2 ml of IM hydrochloric acid and 50 ml of water. Add 50.0 ml of 0.05M disodium edetate and neutralise to methyl red solution with 1 M sodium hydroxide. Heat the solution to boiling, leave on a water-bath for 10 minutes, cool rapidly and add about 50 mg of xylenol orange mixture and 5 g of hexamine. Titrate with 0.05M lead nitrate. Perform a blank determination and make any necessary correction. Each ml of 0.05M disodium edetate is equivatent to 0.008554 g of AI2(SO4)3.AMANTADlNE HYDROCHLORIDEAmantadine Hydrochloride is tricyclo-[3.3.1. 137]dec-1-ylamine hydrochloride. Category: Antiviral; antiparkinsonian Dose: 100 mg daily, increased if necessary to 200 mg daily, in two divideda doses. Description: White or almost white, crystalline powder, sublimes when heated Solubility: Freely soluble in water and in ethanol (95%); soluble in chloroform, practically insoluble in ether. Storage: Store in well-closed containers. STANDARDSAmantadine Hydrochloride contains not less then 98.5 per cent and not more than 101.0 percent of C10H17N,HC1, calculated with reference to the anhydrous substance. Identification Test A may be omitted if tests B, C and D are carried out Tests B and C may be omitted if tests A and D are earned out A: Dissolve 0.1 g in 5 ml of water, add 0.5 ml of SM sodium hydroxide, extract with 5 ml of dichloromethane, fitter the dichloromethane layer through anhydrous sodium sulphate with 2 ml of dichloromethane and evaporate the solution to dryness. The infra-red absorption spectrum of the residue, Appendix 5.4, is concordant with the reference spectrum of amantadine or with the spectrum obtained from amantadine hydrochloride RS treated in the same manner B: Dissolve 0.2 g in 1 ml of 0.1 M hydrochloric acid and add 1 ml of a 50% w/v solution of sodium nitrite; a white precipitate is produced C: To 0.1 g add 1 ml of pyridine. mix, add 0.1 ml of acetic anhydride and boll for about 10 seconds. Pour the hot solution into 10 ml of hydrochloric acid, cool to 5° and filter. The melting range of the residue, after washing with water and drying over phosphorus pentoxide at 60° at a pressure of 1.5 to 2.5 kPa for 1 hour, is between 147° and 151° Appendix 8.8,D: 1 ml of a 10% w/v solution in carbon dioxide free water gives reaction A of chlorides. Appendix 3.1 pH: Between 3.0 and 5.5, determined in a 20% w/v solution. Appendix 8.1 1. Clanty and colour of solution: A 100% w/v solution in carbon dioxide free water is clear, Appendix 6.1, and not more intensety coloured than reference solution YS7, Appendix 6.2. Heavy metals: Not more than 20 ppm, determined by Method A on a solution prepared by dissolving 1.0 g in 1 ml of dilute acetic acid and sufficient water to produce 25 ml. Appendix 3.12. Related substances: Carry out the method for gas chromatography. Appendix 4.2, using 1μ or other suitable volume of the following solution. Dissolve 0.10 g of the substance being examined in 2 ml of water, add 2 ml of a 20% w/v solution of sodium hydroxide and 2 ml of chloroform and shake for 10 minutes. Separate the chloroform layer, dry over anhydrous sodium sulphate and filter. The chromatographic procedure may be carried out using a glass column (1.8 m x 2 mm) containing a packing material prepared in the following manner. Mix 19.5 g of silanised diatomaceous support (such as Chromosorb G/AW/DMCS) with 60 ml of a 0.33% w/v solution of potassium hydroxide in methanol and evaporate the solvent under reduced pressure, while slowly rotating the