EUROPEAN PHARMACOPOEIA 7.1 Oseltamivir phosphate

04/2011:2073 Temperature : Time Temperature OLEYL ALCOHOL (min) (°C) Column 0-1 170 → Alcohol oleicus 1-9 170 210 9-65 210 DEFINITION Injection port 270 Mixture of unsaturated and saturated long-chain fatty alcohols Detector 280 consisting mainly of octadec-9-enol (oleyl alcohol and elaidyl Detection:flameionisation. alcohol; C18H36O; Mr 268.5). It may be of vegetable or animal origin. Injection:1μL. Identify the peaks using the chromatogram obtained with CHARACTERS reference solution (a). Appearance: colourless or light yellow liquid. Relative retention with reference to oleyl alcohol (retention time = about 30 min): palmityl alcohol = about 0.6; linolenyl alcohol = about 0.8; linoleyl alcohol = about 0.9; stearyl IDENTIFICATION alcohol = about 1.1; arachidyl alcohol = about 1.9 (elaidyl A.Hydroxylvalue(seeTests). alcohol co-elutes with oleyl alcohol). B. Composition of fatty alcohols (see Tests). System suitability: reference solution (b): — peak-to-valley ratio: minimum 1.2, where Hp =height above the baseline of the peak due to linoleyl alcohol and TESTS Hv = height above the baseline of the lowest point of the Appearance.Thesubstancetobeexaminedisclear(2.2.1)and curve separating this peak from the peak due to oleyl alcohol. not more intensely coloured than reference solution B6 (2.2.2, Limits: Method II). — palmityl alcohol:maximum8.0percent; Refractive index (2.2.6): 1.458 to 1.461, determined at 25 °C. — stearyl alcohol:maximum5.0percent; Cloud point:maximum10°C. — oleyl alcohol (sum of oleyl and elaidyl alcohols): minimum 80.0 per cent; Introduce about 60 g into a cylindrical flat-bottomed container, 30-33.5 mm in internal diameter and 115-125 mm high. Heat — linoleyl alcohol:maximum3.0percent; to 30 °C, cool, and immerse the container in iced water with — linolenyl alcohol:maximum0.5percent; thesurfacesofthewaterandthesampleatthesamelevel. — arachidyl alcohol:maximum0.3percent. Insert a thermometer and, using it as a stirring rod, begin stirring rapidly and steadily when the temperature falls below 04/2011:2422 20 °C. Keep the thermometer immersed throughout the test, and remove and examine the container at regular intervals. OSELTAMIVIR PHOSPHATE Thecloudpointisthetemperatureatwhichtheimmersed portion of the thermometer, positioned vertically in the centre of the container, is no longer visible when viewed horizontally Oseltamiviri phosphas through the container and sample. Acid value (2.5.1): maximum 1.0, determined on 5.0 g. Hydroxyl value (2.5.3, Method A): 205to215. Saponification value (2.5.6): maximum 2.0. Composition of fatty alcohols. Gas chromatography (2.2.28): use the normalisation procedure. C16H31N2O8P Mr 410.4 Test solution. Mix 25 mg of the substance to be examined with [204255-11-8] 1.0 mL of methylene chloride R. Reference solution (a).Dissolve25mgofeachofarachidyl DEFINITION alcohol R, linolenyl alcohol R, linoleyl alcohol R, oleyl Ethyl (3R,4R,5S)-4-acetamido-5-amino-3-(1-ethylpropoxy)- alcohol R, palmityl alcohol R and stearyl alcohol R in cyclohex-1-ene-1-carboxylate phosphate. methylenechlorideRand dilute to 5 mL with the same solvent. Content: 98.0 per cent to 102.0 per cent (anhydrous substance). Dilute 1 mL of this solution to 5 mL with methylene chloride R. CHARACTERS Reference solution (b).Dissolve10mgoflinoleyl alcohol R and 1 g of oleyl alcohol R in methylene chloride R and dilute Appearance:whiteoralmostwhitepowder. to 40 mL with the same solvent. Solubility: freely soluble in water and in methanol, practically insoluble in methylene chloride. Column: It shows polymorphism (5.9). — material:fusedsilica; IDENTIFICATION — size: l =30m,Ø=0.32mm; A. Specific optical rotation (see Tests). — stationary phase: poly(dimethyl)siloxane R (film thickness B. Infrared absorption spectrophotometry (2.2.24). 1 μm). Comparison: oseltamivir phosphate (impurity B-free) CRS. Carrier gas: helium for chromatography R. If the spectra obtained show differences, dissolve the substance to be examined and the reference substance Flow rate:1mL/min. separately in methanol R, evaporate to dryness and record Split ratio:1:11. new spectra using the residues.

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