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

Consultation DocumentsWHO Drug Information Vol. 24, No. 4, 2010in hydrochloride solution (0.1 mol/l) VS, and rotating the paddle at 75 revolutions perminute. At 30 minutes withdraw a sample of 10 ml of the medium through an in-linefilter and use the filtrate. Prepare standard solution as follows: add a suitable volumeof ethanol (~750 g/l) TS to dissolve a suitable amount of levonorgestrel RS, then adda suitable volume of the dissolution medium to obtain a concentration of 6 µg per ml.Carry out the test as described under 1.14.4 High-performance liquid chromatography,using the chromatographic conditions as described under Assay.For each of the six tablets, calculate the total amount of levonorgestrel (C 21H 28O 2), inthe medium. The amount of levonorgestrel in solution for each tablet is not less than80% of the amount declared on the label. If the amount obtained for one of the sixtablets is less than 80%, repeat the test using a further six tablets; the averageamount for all 12 tablets tested is not less than 75% and no tablet contains less than60%.[Note from Secretariat: possible alternative dissolution method for the 30 µg tablets,which will not use sodium dodecyl sulfate is under investigation.]DextronorgestrelCarry out the test as described under 1.14.4 High-performance liquid chromatography,using a stainless steel column (15 cm x 4.6 mm) packed with particles of silica gel,the surface of which has been modified with chemically bonded octadecylsilyl groups(5 µm). (Hypersil ODS is suitable.) As the mobile phase, use a solution prepared asfollows: dissolve 5.0 g of gamma-cyclodextrin R in 500 ml of water R and dilute to1000.0 ml with methanol R.Prepare the following solutions in a dissolution solvent prepared by mixing 80 volumesof methanol R and 20 volumes of water R. For solution (1) transfer a quantity ofpowdered tablets containing about 3.0 mg of Levonorgestrel to a 25-ml volumetricflask. Add about 15 ml of the dissolution solvent Cheat in a water-bath at 60 °C for 10minutes, shaking occasionally. Allow to equilibrate to room temperature, dilute tovolume with the dissolution solvent and mix. Filter through a 0.45-µm filter. For solution(2), dilute a suitable volume of solution (1) to obtain a concentration of 6 µg ofLevonorgestrel per ml. For solution (3) use 6 µg of levonorgestrel RS per ml. Forsolution (4), use 12 µg of norgestrel RS per ml. For solution (5), use 0.12 µg of LevonorgestrelRS per ml.Operate with a flow rate of 1.5 ml per minute. As a detector, use an ultraviolet spectrophotometerset at a wavelength of 242 nm.Inject 20 µl of solution (3). In the chromatogram obtained with solution (3), the test isnot valid unless the resolution factor between the peaks due to levonorgestrel anddextronorgestrel is at least 1.5.Inject separately 20 µl, each of solutions (1), (2), (3), (4) and (5).In the chromatogram obtained with solution (1) the area of the peak due todextronorgestrel , is not greater than the area of the principal peak in the chromatogramobtained with solution (5) (0.1%).348