» Guanfacine Tablets contain an amount of Guanfacine Hydrochloride (C9H9Cl2N3O·HCl) equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amount of guanfacine (C9H9Cl2N3O).
Packaging and storage Preserve in tight, light-resistant containers.
USP Reference standards 11
A: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that of the Standard preparation as obtained in the Assay.
B: It responds to the Thin-Layer Chromatographic Identification Test 201, the test solution and the Standard solution being prepared at a concentration of 2 mg per mL in methanol, and a solvent system consisting of a mixture of ethyl acetate, glacial acetic acid, and water (5:2:2) being used.
Medium: water; 500 mL.
Apparatus 2: 50 rpm.
Time: 45 minutes.
Procedure Determine the amount of C9H9Cl2N3O dissolved, employing the procedure set forth in the Assay and making any necessary modifications.
Tolerances Not less than 75% (Q) of the labeled amount of C9H9Cl2N3O is dissolved in 45 minutes.
Uniformity of dosage units 905: meet the requirements.
pH 2.5 Diethylamine phosphate solution Add 10.3 mL of diethylamine to about 70 mL of water. Adjust with phosphoric acid to a pH of 2.5, dilute with water to 100 mL, and mix.
Reagent solution Dissolve an accurately weighed quantity of 2,6-dichlorophenylacetic acid in Mobile phase, and dilute quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 18 µg per mL.
Mobile phase Dissolve 600 mg of monobasic potassium phosphate and 3 mL of pH 2.5 Diethylamine phosphate solution in 480 mL of water, and mix. Adjust with 0.2 N sodium hydroxide to a pH of 4.0. While swirling, add 520 mL of acetonitrile. Filter and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Internal standard solution Prepare a solution of butylparaben in Mobile phase containing 0.5 mg per mL.
Standard preparation Dissolve an accurately weighed quantity of USP Guanfacine Hydrochloride RS in Mobile phase to obtain a solution having a known concentration of about 0.23 mg per mL. Transfer 5.0 mL of this solution to a 25-mL volumetric flask, and add 5.0 mL each of the Reagent solution and the Internal standard solution. Dilute with Mobile phase to volume, and mix.
Assay preparation Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 10 mg of guanfacine, to a 100-mL volumetric flask. Add 50 mL of Mobile phase, and heat on a steam bath for 5 minutes. Cool to room temperature, dilute with Mobile phase to volume, and mix. Transfer 10.0 mL of this solution to a 25-mL volumetric flask, add 5.0 mL of Internal standard solution, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 220-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.4 for guanfacine, 0.6 for 2,6-dichlorophenylacetic acid, and 1.0 for butylparaben; the resolution, R, between guanfacine and 2,6-dichlorophenylacetic acid is not less than 1.5, and the resolution, R, between 2,6-dichlorophenylacetic acid and butylparaben is not less than 1.5; and the relative standard deviation for replicate injections 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, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of guanfacine (C9H9Cl2N3O) in the portion of Tablets taken by the formula:
(246.09/282.55)(0.25C)(RU / RS)in which 246.09 and 282.55 are the molecular weights of guanfacine and guanfacine hydrochloride, respectively; C is the concentration, in µg per mL, of USP Guanfacine Hydrochloride RS in the Standard preparation; and RU and RS are the peak response ratios of guanfacine to butylparaben obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 3392Pharmacopeial Forum: Volume No. 27(4) Page 2736