17-Hydroxy-6,7:15,16-dimethylene-3-oxo-17-pregn-4-ene-21-carboxylic acid, -lactone [67392-87-4].
» Drospirenone contains not less than 98.0 percent and not more than 102.0 percent of C24H30O3, calculated on the anhydrous, solvent-free basis.
Packaging and storage Preserve in tight containers, and store at controlled room temperature.
B: The retention time of the major peaks in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Melting range, Class 1 741: between 198 and 203. [noteDry over silica gel for not less than 24 hours prior to testing.]
Specific rotation 781S: between 186 and 196 on the anhydrous and solvent-free basis (10 mg per mL in methanol).
Water, Method I 921: not more than 0.2%.
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method II 231: not more than 0.002%.
Limit of 1,2-dimethoxyethane and diisopropyl ether (if present)
Standard solution Prepare a solution of 1,2-dimethoxyethane and diisopropyl ether in dimethylformamide to obtain a solution having known concentrations of about 0.1 mg per mL and 0.05 mg per mL, respectively.
Test solution Dissolve an accurately weighed portion of Drospirenone in dimethylformamide to obtain a solution having a known concentration of about 50 mg per mL.
Chromatographic system (see Chromatography 621) The gas chromatograph is equipped with a headspace injector, a flame-ionization detector, and a 0.25-mm × 30-m capillary column coated with a 1.4-µm film of liquid phase G43. The column temperature is programmed according to the following steps: it is held at 40 for 10 minutes, then increased at a rate of 5 per minute to 70; it is then increased at a rate of 30 per minute to 220. The injection port temperature is maintained at 160, and the detector temperature is maintained at 250. The carrier gas is helium, flowing at a rate of about 32 ± 8 cm per second. [noteFor pressure-controlled systems, a column pressure of approximately 130 kPa will be necessary.] Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.6 for diisopropyl ether and 1.0 for 1,2-dimethoxyethane; and the relative standard deviation for the Standard solution is not more than 4.0%.
Procedure Transfer 2.0 mL each of the Test solution and the Standard solution to separate headspace vials, and seal. The vials are maintained at 80 for 60 minutes prior to headspace injection. Record the chromatograms, and measure the peak areas for the 1,2-dimethoxyethane and diisopropyl ether peaks. Separately calculate the percentage of 1,2-dimethoxyethane and diisopropyl ether in the portion of Drospirenone taken by the formula:
100(CS /CU)(rU / rS)in which CS is the concentration, in mg per mL, of 1,2-dimethoxyethane or diisopropyl ether in the Standard solution; CU is the concentration, in mg per mL, of Drospirenone in the Test solution; and rU and rS are the 1,2-dimethoxyethane or diisopropyl ether peak areas in the chromatograms obtained from the Test solution and the Standard solution, respectively: not more than 0.2% of 1,2-dimethoxyethane and 0.1% of diisopropyl ether are found.
Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system Prepare as directed in the Assay.
Standard solution Prepare as directed for the Standard preparation in the Assay.
Test solution Prepare as directed for the Assay preparation in the Assay.
Procedure Separately inject equal volumes (about 10 µL) of the Standard solution, the Test solution, and the Diluent into the chromatograph, and record the chromatograms. Calculate the percentage of each impurity in the portion of Drospirenone taken by the formula:
100(ri / rs)in which ri is the peak area for each impurity; and rs is the sum of the responses of all the peaks. Disregard peaks that are less than 0.05% of the drospirenone peak. Not more than 0.1% of any individual impurity is found; and not more than 0.4% of total impurities is found.
Solution A Use water.
Solution B Use acetonitrile.
Mobile phase Use variable mixtures of Solution A and Solution B, as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent Prepare a degassed mixture of water and acetonitrile (1:1).
Standard preparation Dissolve accurately weighed quantity of USP Drospirenone RS in Diluent to obtain a solution having known concentration of about 2 mg per mL.
Assay preparation Transfer about 20 mg of Drospirenone, accurately weighed, to a 10-mL volumetric flask, dissolve in and dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 245-nm detector and a 4.0-mm × 25-cm column containing 5-µm packing L1 that is maintained at a constant temperature of about 30. The flow rate is about 1.5 mL per minute. The chromatograph is programmed as follows.
Procedure Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the response for the drospirenone peak. Calculate the quantity, in mg, of C24H30O3 in the portion of Drospirenone taken by the formula:
10C(rU / rS)in which C is the concentration, in mg per mL, of USP Drospirenone RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information Please check for your question in the FAQs before contacting USP.Chromatographic Column
USP32NF27 Page 2220Pharmacopeial Forum: Volume No. 32(3) Page 787
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.