WHO Drug Information Vol. 24, No. 4, 2010

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Consultation DocumentsWHO Drug Information Vol. 24, No. 4, 2010Operate with a flow rate of 1.0 ml per minute. As a detector use an ultraviolet spectrophotometerset at a wavelength of about 294 nm.Inject 20 µl of solution (3). The test is not valid unless the resolution factor betweenthe peaks due to impurity E and Levofloxacin is at least 2.Inject separately 20 µl each of solutions (1) and (2) and of the dissolution solvent inthe chromatographic system.In the chromatogram obtained with solution (1), the following peaks are eluted at thefollowing relative retention with reference to Levofloxacin (retention time about 17minutes): impurity B about 0.36; impurity C about 0.57; impurity D about 0.75; impurityE about 0.91; impurity F about 1.50.Measure the areas of the peak responses in the chromatograms obtained with solutions(1) and (2). Calculate the content of Levofloxacin (C 18H 20FN 3O 4).B. Weigh and powder 20 tablets. Transfer a quantity of the powdered tablets containingabout 25 mg of Levofloxacin, accurately weighed, to a 50-ml volumetric flask. Addabout 20 ml of hydrochloric acid (~4 g/l) TS, sonicate for about 5 minutes, allow to coolto room temperature and make up to the volume using the same solvent. Filter aportion of this solution through a 0.45-µm filter, discarding the first few ml of the filtrate.Dilute 1.0 ml of this solution to 100.0 ml using water R. Measure the absorbance (1.6)of a 1-cm layer of this solution at the maximum at about 294 nm. Calculate the content1%of Levofloxacin in the tablets using an absorptivity value of 91.2 ( A = 912).Impurities. The impurities limited by the requirements of this monograph includeimpurities B to F listed in the monograph for Levofloxacin.* * *New reagent to be added to The International Pharmacopoeia:Hydrochloric acid (~4 g/l) TS.Dilute 10 ml of hydrochloric acid (~420 g/l) TS with sufficient water to produce 1000 ml(approximately 0.1 mol/l).1 cmLevonorgestrel tabletsDraft proposal for The International Pharmacopoeia (September2010). Please address any comments to Quality Assurance andSafety: Medicines, World Health Organization, 1211 Geneva 27,Switzerland. Fax +41227914730 or e-mail to mendyc@who.int. Asubscriber mailing list is now available to speed up consultation.For more information please contact bonnyw@who.int.Category. Contraceptive.Storage. Levonorgestrel tablets should be kept in a well-closed container, protectedfrom light.346
WHO Drug Information Vol. 24, No. 4, 2010Consultation DocumentsAdditional information. Strength in the current WHO Model List of Essential Medicines:30 µg, 750 µg, 1.5 mg.Comply with the monograph for “Tablets”.REQUIREMENTSDefinition. Levonorgestrel tablets contain Levonorgestrel. They contain not less than90.0% and not more than 110.0% of the amount of levonorgestrel (C 21H 28O 2) stated onthe label.Identity testsEither tests A and B or tests A and C may be applied.A. To a quantity of the powdered tablets containing 37.5 mg of Levonorgestrel, add 5quantities of dichloromethane R, each of 40 ml. After each addition, stir thoroughlyand filter through a sintered-glass filter (G4). Wash the residue and the filter withdichloromethane R, combine the filtrates, evaporate to dryness on a water-bath withthe aid of a stream of air and allow to cool. Dissolve the residue in 5 ml of dichloromethaneR and measure the optical rotation. The optical rotation of the resultingsolution is not less than -0.18°.B. Carry out test B.1 or, where UV detection is not available, test B.2.B.1 Carry out the test as described under 1.14.1 Thin-layer chromatography, usingsilica gel R6 as the coating substance and a mixture of 7 volumes of cyclohexane Rand 3 volumes of acetone R as the mobile phase. Apply separately to the plate 10 l ofeach of the following two solutions in acetonitrile R. For solution (A) shake a quantityof the powdered tablets containing 1.5 mg of Levonorgestrel with 5 ml, filter, and usethe clear filtrate. For solution (B) use 0.30 mg of levonorgestrel RS per ml. Afterremoving the plate from the chromatographic chamber, allow it to dry exhaustively inair or in a current of cool air. Examine the chromatogram in ultraviolet light at 254 nm.The principal spot obtained with solution A corresponds in position, appearance andintensity to that obtained with solution B.B.2 Carry out the test as described under 1.14.1 Thin-layer chromatography, using theconditions described under test B.1 but using silica gel R5 as the coating substance.Spray with a mixture of equal volumes of sulfuric acid TS and ethanol (~750 g/l) TS.Heat the plate for a few minutes at 105 °C. Examine the chromatogram in daylight.The principal spot obtained with solution A corresponds in position, appearance andintensity to that obtained with solution B.C. See the method described below under the test for Dextronorgestrel. The retentiontime of the principal peak in the chromatogram obtained with solution (2) is similar tothat in the chromatogram obtained with the solution (3).Dissolution testCarry out the test as described under 5.5 Dissolution test for solid oral dosage forms,using as the dissolution medium, 500 ml of 0.1% solution of sodium dodecyl sulfate R347
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WHO Drug Information Vol. 24, No. 4, 2010

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