吐溫80英國藥典英文.doc

enan111，密碼1988342、消癌平注射液中吐溫-80用量的研究及質(zhì)量控制2.1建立消癌平注射液中吐溫-80含量的測定方法2.2建立吐溫-80純度的測定方法2.3不同廠家不同純度的吐溫-80增容效果及安全性評價 1、消癌平注射液中高分子雜質(zhì)去除方法研究1.1建立GPC法測定消癌平注射液中高分子物質(zhì)的方法1.2超濾前后高分子物質(zhì)的去除效果研究Polysorbate 80Polyoxyethylene 20 Sorbitan Mono-oleate (Ph Eur monograph 0428) 9005-65-6 Ph Eur DEFINITION Polysorbate 80 is a mixture of partial esters of various fatty acids, mainly oleic acid, and sorbitol and its anhydrides copolymerised with approximately 20 moles of ethylene oxide for each mole of sorbitol and sorbitol anhydrides. The fatty acid fraction can be of vegetable or animal origin. It contains not less than 60.0 per cent of oleic acid and not less than 90.0 per cent and not more than 110.0 per cent of the content stated on the label. PRODUCTION 2-Chloroethanol, ethylene glycol and diethylene glycol Not more than 10 ppm of 2-chloroethanol and not more than a total of 0.25 per cent for ethylene glycol and diethylene glycol, determined by head-space gas chromatography (2.2.28), using themethod of standard additions. Test solution Place 50 mg of the substance to be examined in a 20 ml vial, add 2.0 ml of 2-propanol R and close immediately. Allow to stand for about 2 min and in any case not more than 5 min. Reference solution Place 50 mg of the substance to be examined in a 20 ml vial, add 2.0 ml of a solution containing, in 2-propanol R, 0.25 mg/ml of 2-chloroethanol R, 31.25 mg/ml of ethylene glycol R and 31.25 mg/ml of diethylene glycol R and close immediately. Allow to stand for about 2 min and in any case not more than 5 min. The chromatographic procedure may be carried out using: a purge and trap head space sampler, assembled before the chromatographic system using a stainless steel precolumn 13.6 mm long and 4 mm in internal diameter packed with ethylvinylbenzene-divinylbenzene copolymer R as trap column and helium for chromatography R as the carrier gas at a flow rate of 20 ml/min and an additional 20 ml/min as auxiliary gas. Place the vials separately on a water-bath at 110 C and begin purging within 5 min, whilst maintaining the trap column at 50 C; continue purging for 40 min. Then raise the temperature of the trap column to 210 C and inject for 5 min in the chromatographic system, a fused-silica column 30 m long and 0.53 mm in internal diameter, the internal wall of which is coated with macrogol 20 000 for chromatography R (film thickness 1 mm), helium for chromatography R as the carrier gas at a linear velocity of 60 cm/s, a flame-ionisation detector. Calculate the content of 2-chloroethanol, ethylene glycol and diethylene glycol from the areas of the peaks and the concentration of the solutions. CHARACTERS An oily, yellowish or brownish-yellow, clear liquid, miscible with water, with ethanol, with ethyl acetate and with methanol, practically insoluble in fatty oils and in liquid paraffin. It has a relative density of about 1.08. It has a viscosity of about 400 mPas at 25 C. IDENTIFICATION First identification B, C. Second identification A, D, E. A. Dissolve 0.5 g in water R at about 50 C and dilute to 10 ml with the same solvent. The solution produces a copious foam on shaking. Add 0.5 g of sodium chloride R and heat the solution to boiling. The resulting cloudiness disappears during cooling to about 50 C. B. Examine by infrared absorption spectrophotometry (2.2.24), comparing with the Ph.Eur. reference spectrum of polysorbate 80 at the following wavelengths: 720 cm-1, 1110 cm-1, 1250 cm-1, 1300 cm-1, 1350 cm-1, 1740 cm-1, 2850 cm-1, 2920 cm-1 and 3500 cm-1. C. It complies with the limits of the assay. D. To 2 ml of a 50 g/l solution, add 0.5 ml of bromine water R. The mixture is decolorised. E. Dissolve 0.1 g in 5 ml of methylene chloride R. Add 0.1 g of potassium thiocyanate R and 0.1 g of cobalt nitrate R. Stir with a glass rod. The solution becomes blue. TESTS Acid value (2.5.1) Not more than 2.0, determined on 5.0 g dissolved in 50 ml of the prescribed mixture of solvents. Hydroxyl value (2.5.3, Method A) 65 to 80, determined on 2.0 g. Peroxide value (2.5.5) Not more than 10. Saponification value (2.5.6) 45 to 55, determined on 2.0 g. Use 15.0 ml of 0.5 M alcoholic potassium hydroxide and dilute with 50 ml of water R before carrying out the titration. Ethylene oxide and dioxan (2.4.25, System A) Not more than 1 ppm of ethylene oxide and not more than 10 ppm of dioxan. When determining the dioxan content, apply a correction factor of 1/5 to the calculation. Heavy metals (2.4.8) 2.0 g complies with limit test C for heavy metals (10 ppm). Prepare the standard using 2 ml of lead standard solution (10 ppm Pb) R. Water (2.5.12) Not more than 3.0 per cent, determined on 1.000 g by the semi-micro determination of water. Sulphated ash Not more than 0.25 per cent. To 2.00 g in a silica or platinum crucible, add 0.5 ml of sulphuric acid R and heat on a water-bath for 2 h. Carefully ignite at a low temperature until thoroughly charred. Add to the carbonised mass 2 ml of nitric acid R and 0.25 ml of sulphuric acid R, then cautiously heat until white fumes are evolved and ignite at 600 C until all black particles have disappeared. Allow to cool, weigh and repeat the ignition for periods of 15 min to constant mass. Pyrogens (2.6.8) If intended for use in the manufacture of parenteral dosage forms without a further appropriate procedure for the removal of pyrogens, it complies with the test for pyrogens. Inject per kilogram of the rabbits mass 5.0 ml of a solution containing 2 mg/ml of the substance to be examined in a 9 g/l solution of sodium chloride R. ASSAY Examine by gas chromatography (2.2.28). Test solution Dissolve 0.10 g of the substance to be examined in 2 ml of methanolic sodium hydroxide solution R1 in a 25 ml conical flask and boil under a reflux condenser for 30 min. Add 2.0 ml of a 140 g/l solution of boron trifluoride R in methanol R through the condenser and boil for 30 min. Add 4 ml of heptane R through the condenser and boil for 5 min. Cool and add 10.0 ml of saturated sodium chloride solution R, shake for about 15 s and add a quantity of saturated sodium chloride solution R such that the upper layer is brought into the neck of the flask. Collect 1 ml of the upper layer and dry it over anhydrous sodium sulphate R. Reference solution Dissolve 0.02 g of methyl oleate R in heptane R and dilute to 10 ml with the same solvent. Dilute 1 ml of the solution to 50.0 ml with heptane R. The chromatographic procedure may be carried out using: a fused-silica column 30 m long and 0.32 mm in internal diameter, the internal wall of which is coated with macrogol 20 000 for chromatography R (film thickness 0.5 mm), helium for chromatography R as the carrier gas at a linear velocity of 50 cm/s, a flame-