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

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Consultation DocumentsWHO Drug Information Vol. 24, No. 4, 2010AssayCarry out the test as described under 1.14.4 High-performance liquid chromatography,using a stainless steel column (25 cm x 4.6 mm) packed with base-deactivated particlesof silica gel the surface of which has been modified with chemically bondedoctadecylsilyl groups (5 m).The mobile phases for gradient elution consist of a mixture of Mobile phase A andMobile phase B, using the following conditions:Mobile phase A:Mobile phase B:5 volumes of potassium dihydrogen phosphate (27.2 g/l) TSand 95 volumes of water R.70 volumes of acetonitrile R, 5 volumes of potassium dihydrogenphosphate (27.2 g/l) TS and 25 volumes of water R.Time Mobile phase A Mobile phase B Comments(min) (% v/v) (% v/v)0–9 93 7 Isocratic9–15 93 to 0 7 to 100 Linear gradient15–19 0 100 Isocratic19–19.1 0 to 93 100 to 7 Return to initialcomposition19.1–30 93 7 Re-equilibrationAfter preparation, keep the solutions at about 6 °C, or use an injector with cooling.Prepare the following solutions using a mixture of 20 volumes of acetonitrile R and 80volumes of water R as a diluent. For solution (1) weigh and powder 20 tablets. Dispersea quantity of the powder containing about 10 mg of Tenofovir disoproxil fumarate,accurately weighed in 100 ml of the diluent and filter. For solution (2) use 0.2 mgof efavirenz RS, 0.1 mg of tenofovir disoproxil fumarate RS and 66.7 µg of emtricitabineRS per ml of diluent. For solution (c) use 0.02 mg of fumaric acid R per ml of waterR.If necessary adapt the concentration of solution (2) according to the ratio of Efavirenz,Emtricitabine and Tenofovir disoproxil fumarate in the tablets.Operate with a flow rate of 1.0 ml per minute. As a detector use an ultraviolet spectrophotometerset at a wavelength of 280 nm.Maintain the column temperature at 35 °C.Inject separately 20 µl each of solutions (1), (2) and (3).The test is not valid unless in the chromatograms obtained with solutions (1) and (2),four principal peaks, that elute at the following retention times, are shown: fumarate(about 2.5 minutes), emtricitabine (about 9 minutes), tenofovir disoproxil (about 18minutes) and efavirenz (about 22 minutes).326
WHO Drug Information Vol. 24, No. 4, 2010Consultation DocumentsCalculate the content of efavirenz (C 14H 9ClF 3NO 2), emtricitabine (C 8H 10FN 3O 3S) andtenofovir disoproxil fumarate (C 19H 30N 5O 10P,C 4H 4O 4) in the tablets.Emtricitabinum capsulaeEmtricitabine capsulesDraft 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. Antiretroviral (Nucleoside Reverse Transcriptase Inhibitor).Storage. Emtricitabine capsules should be kept in a tightly closed container.Additional information. Strength in the current WHO Model List of Essential Medicines:200 mg Emtricitabine.REQUIREMENTSComply with the monograph for “Capsules”.Definition. Emtricitabine capsules contain Emtricitabine. They contain not less than90.0% and not more than 110.0% of the amount of emtricitabine (C 8H 10FN 3O 3S) statedon the label.Identity testsEither tests A and B or test C may be applied.A. Carry out test A.1 or, when UV detection is not available, test A.2.A.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 90 volumes of dichloromethaneR, 10 volumes of methanol R and 3 volumes of glacial acetic acid R as the mobilephase. Apply separately to the plate 5 µl of each of the following two solutions inmethanol R. For solution (A) disperse a quantity of the contents of the capsules toobtain a concentration of 5 mg of Emtricitabine per ml, filter and use the filtrate. Forsolution (B) use 5 mg of emtricitabine RS per ml. After removing the plate from thechromatographic chamber, allow it to dry exhaustively in air or in a current of air.Examine the chromatogram in ultraviolet light (254 nm).The principal spot obtained with solution A corresponds in position, appearance, andintensity with that obtained with solution B.A.2 Carry out the test as described under 1.14.1 Thin-layer chromatography, using theconditions described above under test A.1 but using silica gel R5 as the coatingsubstance. Stain the plate with iodine vapour and examine in daylight.327
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