Sodium-Valproate-5571[英国药典BP2009]

Sodium Valproate General Notices(Ph Eur monograph 0678)IDENTIFICATIONA. Infrared absorption spectrophotometry (2.2.24).Comparison sodium valproate CRS.If the spectra obtained in the solid state show differences, record new spectra using discs prepared by placing 50 µl of a 100 g/l solution in methanol R on a disc of potassium bromide R and evaporating the solvent in vacuo. Examine immediately.B. Examine the chromatograms obtained in the test for related substances.Results The principal peak in the chromatogram obtained with test solution (b) is similar in retention time to the principal peak in the chromatogram obtained with reference solution (b).C. 2 ml of solution S (see Tests) gives reaction (a) of sodium (2.3.1) .TESTSSolution SDissolve 1.25 g in 20 ml of distilled water R in a separating funnel, add 5 ml of dilute nitric acid R and shake. Allow the mixture to stand for 12 h. Use the lower layer.Appearance of solutionThe solution is not more opalescent than reference suspension II (2.2.1) and not more intensely coloured than reference solution Y6(2.2.2, Method II).Dissolve 2.0 g in water R and dilute to 10 ml with the same solvent.Acidity or alkalinityDissolve 1.0 g in 10 ml of water R. Add 0.1 ml of phenolphthalein solution R . Not more than 0.75 ml of 0.1 M hydrochloric acid or 0.1 M sodium hydroxide is required to change the colour of the indicator.Related substancesGas chromatography (2.2.28).Internal standard solution Dissolve 10 mg of butyric acid R in heptane R and dilute to 200 ml with the same solvent.Test solution (a) Dissolve 0.500 g of the substance to be examined in 10 ml of water R . Add 5 ml of dilute sulphuric acid R and shake with 3 quantities, each of 20 ml, of heptane R. Add 10.0 ml of the internal standard solution to the combined upper layers, shake with anhydrous sodium sulphate R , filter and evaporate the filtrate, at a temperature not exceeding 30 °C, using a rotary evaporator. Take up the residue with heptane R and dilute to 10.0 ml with the same solvent. Dilute 1.0 ml of this solution to 10.0 ml with heptane R .Test solution (b) Dissolve 40 mg of the substance to be examined in 100 ml of water R . To 10 ml of this solution add 0.5 ml of dilute sulphuric acid R and shake with 3 quantities, each of 5 ml, of heptane R . Shake with anhydrous sodium sulphate R, filter and evaporate the filtrate, at a temperature not exceeding 30 °C, to a volume of about 10 ml, using a rotaryevaporator.Reference solution (a) Dissolve 20 mg of 2-(1-methylethyl)pentanoic acid CRS (impurity C) in 5.0 ml of test solution (b) and dilute to 10 ml with heptane R . Dilute 1 ml of this solution to 10 ml with heptane R.Reference solution (b) Prepare as prescribed for test solution (b), using sodium valproate CRS instead of the substance to be examined.Column:— material: wide-bore fused silica;— size: l = 30 m, Ø = 0.53 mm;— stationary phase: macrogol 20 000 2-nitroterephthalate R (film thickness 0.5 µm). Carrier gas helium for chromatography R.Flow rate 8 ml/min.Temperature:Detection Flame ionisation.Injection 1 µl.System suitability Reference solution (a):— resolution: minimum 3.0 between the peaks due to impurity C and valproic acid.Limits Test solution (a):— any impurity: for each impurity, not more than the area of the peak due to the internal standard (0.1 per cent);— total: not more than 3 times the area of the peak due to the internal standard (0.3 per cent);— disregard limit: 0.1 times the area of the peak due to the internal standard (0.01 per cent).Chlorides (2.4.4)Maximum 200 ppm.To 5 ml of solution S add 10 ml of water R.Sulphates (2.4.13)Maximum 200 ppm, determined on Solution S.Heavy metals (2.4.8)Maximum 20 ppm.1.0 g complies with test C. Prepare the reference solution using 2 ml of lead standard solution (10 ppm Pb) R.Loss on drying (2.2.32)Maximum 2.0 per cent, determined on 1.000 g by drying in an oven at 105 °CASSAYDissolve 0.1500 g in 25 ml of anhydrous acetic acid R . Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20) .1 ml of 0.1 M perchloric acid is equivalent to 16.62 mg of C8H15NaO2.STORAGEIn an airtight container.IMPURITIESA. R = R′ = H: pentanoic acid (valeric acid),B. R = H, R′ = CH2-CH3: (2RS)-2-ethylpentanoic acid,C. R = H, R′ = CH(CH3)2: (2RS)-2-(1-methylethyl)pentanoic acid,D. R = R′ = CH2-CH2-CH3: 2,2-dipropylpentanoic acid,E. R = R′ = H: pentanamide (valeramide),F. R = H, R′ = CH2-CH2-CH3: 2-propylpentanamide,G. R = R′ = CH2-CH2-CH3: 2,2-dipropylpentanamide,Soft SoapGeneral NoticesPreparationSoap SpiritDEFINITIONSoft Soap is soap made by the interaction of potassium hydroxide or sodium hydroxide with a suitable vegetable oil or oils or with fatty acids derived there from. It yields not less than44.0% of fatty acids. It may be coloured with chlorophyll or not more than 0.015% of a suitable green soap dye.CHARACTERISTICSA yellowish white to green or brown, unctuous substance.Soluble in water and in ethanol (96%).TESTSChlorides and other ethanol-insoluble substancesDissolve 5 g in 100 ml of hot ethanol (96%) previously neutralised to phenolphthalein solution R1, filter through a dried and tared filter, wash the residue thoroughly with hot neutralised ethanol (96%) and dry to constant weight at 105°. The residue weighs not more than 0.15 g. Free fatty acid or alkali hydroxideBoil 250 ml of ethanol (96%) to remove carbon dioxide, add 0.5 ml of phenolphthalein solution R1, allow to cool to 70° and neutralise, if necessary, with 0.1M sodium hydroxide VS or 0.05M sulphuric acid VS. To 100 ml of the neutral ethanol add 10 g of the substance being examined and dissolve it as quickly as possible by heating under a reflux condenser. Cool to 70° and, if the solution is not pink, titrate at 70° with 0.1M sodium hydroxide VS; not more than 0.2 ml is required. If the solution is pink add, in a thin stream, 5 ml of hot barium chloride solution previously neutralised to phenolphthalein solution R1, mix thoroughly and titrate with 0.1M hydrochloric acid VS until the pink colour disappears; not more than 1.0 ml is required.Total free alkaliTo 100 ml of the neutral ethanol prepared as described in the test for Free fatty acid or alkali hydroxide add 10 g of the substance being examined and dissolve it as quickly as possible by heating under a reflux condenser. Add immediately 3 ml of 0.5M sulphuric acid VS and boil under a reflux condenser on a water bath for at least 10 minutes. If the solution is not pink, cool to 70° and titrate with 1M sodium hydroxide VS until a pink colour is produced. The volume of 0.5M sulphuric acid VS neutralised by the substance being examined is not more than 1.0 ml.Unsaponifiable matter and unsaponified neutral fatDissolve 5 g in 80 ml of a mixture of 50 ml of ethanol (96%) and 100 ml of water, without。