(gris'' ee oh ful' vin).
Spiro[benzofuran-(3H),1¢-2cyclohexene]-3,4¢-dione, 7-chloro-2¢,4,6-trimethoxy-6¢-methyl-, (1¢S-trans)-.
7-Chloro-2¢,4,6-trimethoxy-6¢-methylspiro[benzofuran-2(3H), 1¢-cyclohexene]-3,4¢-dione [126-07-8].
» Griseofulvin has a potency of not less than 900 µg of C17H17ClO6 per mg.
Packaging and storage Preserve in tight containers.
USP Reference standards 11
USP Griseofulvin Permeability Diameter RS
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Melting range 741: between 217 and 224.
Specific rotation 781S: between +348 and +364.
Test solution: 10 mg per mL, in dimethylformamide.
Crystallinity 695: meets the requirements.
Loss on drying 731 Dry about 100 mg, accurately weighed, in a capillary-stoppered bottle in vacuum at a pressure not exceeding 5 mm of mercury at 60 for 3 hours: it loses not more than 1.0% of its weight.
Residue on ignition 281: not more than 0.2%.
Permeability diameter Determine the apparent particle size in µm by the air-permeation method, using a suitable subsieve sizer. Weigh 1.819 ± 0.001 g of Griseofulvin, and transfer to the compression tube of the apparatus. Compact with moderate pressure so that a uniform porosity is achieved. Pass dry compressed air through the tube, and measure the air pressure with a water manometer. Read the porosity, and calculate the apparent particle size from the instrument equation. Repeat the porosity readings at successively higher degrees of compaction until the apparent particle size reaches a minimum value. Calculate the observed permeability diameter, in square meters per g, taken by the formula:
6 / (1.455MF)in which M is the minimum apparent particle size; and F is a factor, obtained from the accompanying table, interpolation being used if necessary, to correct the apparent particle size to the true particle size at a given porosity reading.
OU (AS / OS)in which OU is the observed permeability diameter of the specimen, AS is the assigned permeability diameter of USP Griseofulvin Permeability Diameter RS, and OS is the observed permeability diameter of USP Griseofulvin Permeability Diameter RS: it is between 1.3 and 1.7 square meters per g.
Heavy metals, Method II 231: 0.0025%.
Mobile phase Prepare a suitable filtered mixture of water, acetonitrile, and tetrahydrofuran (60:35:5). Degas for 5 minutes before use, and stir continuously during use. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation Dissolve an accurately weighed quantity of USP Griseofulvin RS in methanol to obtain a solution having a known concentration of about 1.25 mg per mL. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix. This solution contains about 0.125 mg of USP Griseofulvin RS in each mL.
Assay preparation Transfer about 62 mg of Griseofulvin, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with methanol to volume, and mix. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column that contains packing L10. The flow rate is about 1 mL per minute. The relative standard deviation for replicate injections of Standard preparation is not more than 2.0%.
Procedure Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, and measure the peak responses for the major peaks. Calculate the quantity, in µg of C17H17ClO6, in each mg of the Griseofulvin taken by the formula:
500(CP / WU)(rU / rS)in which C is the concentration, in mg per mL, of USP Griseofulvin RS in the Standard preparation; P is the content, in µg of C17H17ClO6 per mg, of USP Griseofulvin RS; WU is the quantity, in mg, of Griseofulvin taken; and rU and rS are the griseofulvin peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 3378