Clonidine Hydrochloride and Chlorthalidone Tablets
» Clonidine Hydrochloride and Chlorthalidone Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of chlorthalidone (C14H11ClN2O4S) and not less than 90.0 percent and not more than 110.0 percent of the labeled amount of clonidine hydrochloride (C9H9Cl2N3·HCl).
Packaging and storage Preserve in well-closed containers.
USP Reference standards 11
A: Transfer an amount of powdered Tablets, equivalent to about 3 mg of clonidine hydrochloride, to a beaker, add 30 mL of water, stir for 5 minutes, and filter, using a medium-porosity, sintered-glass funnel. Transfer the filtrate to a separator, add 5 mL of 0.1 N sodium hydroxide, and extract with 20 mL of chloroform, collecting the chloroform extract in a separator. Extract the chloroform phase with 15 mL of 0.01 N hydrochloric acid, collecting the acid extract in a beaker. Remove any residual chloroform from the acid extract by heating on a steam bath: the UV absorption spectrum of the solution so obtained exhibits maxima and minima at the same wavelengths as that of a similar solution of USP Clonidine Hydrochloride RS, concomitantly measured.
B: Transfer 10 powdered Tablets to a 50-mL beaker, add 10 mL of methanol, boil on a steam bath for 5 minutes, and filter. Add 20 mL of water to the filtrate, and boil on a steam bath for 5 minutes under a current of air. Cool, with stirring, in ice until crystals form, filter the crystals, and dry at 105 for 1 hour: the IR absorption spectrum of a mineral oil dispersion of the dried crystals exhibits maxima only at the same wavelengths as that of a similar preparation of USP Chlorthalidone RS.
C: The retention times of the chlorthalidone and clonidine hydrochloride peaks in the chromatogram of the Assay preparation correspond to those of the Standard preparation as obtained in the Assay.
Medium: water; 900 mL.
Apparatus 2: 100 rpm.
Time: 60 minutes.
Procedure Pipet 20 mL of a centrifuged portion of the solution under test into a 25-mL volumetric flask, and dilute with 0.5% monobasic ammonium phosphate solution to volume. Use the resulting solution as the Assay preparation. Determine the amounts of chlorthalidone (C14H11ClN2O4S) and clonidine hydrochloride (C9H9Cl2N3·HCl) dissolved, employing the procedure set forth in the Assay, making any necessary volumetric adjustments.
Tolerances Not less than 50% (Q) of the labeled amount of C14H11ClN2O4S and not less than 80% (Q) of the labeled amount of C9H9Cl2N3·HCl are dissolved in 60 minutes.
Uniformity of dosage units 905: meet the requirements for Content Uniformity with respect to both chlorthalidone and clonidine hydrochloride.
Mobile phase Dissolve 800 mg of monobasic ammonium phosphate in 800 mL of water, add 100 mL of methanol and 100 mL of acetonitrile, mix, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation Dissolve an accurately weighed quantity of USP Clonidine Hydrochloride RS in 0.1% monobasic ammonium phosphate solution, and dilute quantitatively with the same solvent to obtain a solution having a known concentration of about 1500J µg per mL, J being the ratio of the labeled amount, in mg, of clonidine hydrochloride to the labeled amount, in mg, of chlorthalidone per Tablet (Solution P). Transfer about 15 mg of USP Chlorthalidone RS, accurately weighed, to a 100-mL volumetric flask, dissolve in 10 mL of methanol, add 25 mL of 0.1% monobasic ammonium phosphate solution and 10.0 mL of Solution P, dilute with 0.1% monobasic ammonium phosphate solution to volume, and mix to obtain a solution having known concentrations of about 150J µg of USP Clonidine Hydrochloride RS per mL and about 150 µg of USP Chlorthalidone RS per mL.
Assay preparation Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 15 mg of chlorthalidone, to a 100-mL volumetric flask, add 10 mL of methanol, and sonicate for 5 minutes. Add 40 mL of 0.1% monobasic ammonium phosphate solution, sonicate until the solution is free from agglomerates, allow to cool to ambient temperature, dilute with 0.1% monobasic ammonium phosphate solution to volume, mix, and centrifuge.
Chromatographic system (see Chromatography 621)The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 10-cm column that contains packing L7. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.2 for clonidine hydrochloride and 1.0 for chlorthalidone; the resolution, R, between the clonidine hydrochloride and chlorthalidone peaks is not less than 3; and the relative standard deviation for replicate injections is not more than 2%.
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 clonidine hydrochloride (C9H9Cl2N3·HCl) in the portion of Tablets taken by the formula:
0.1C(rU / rS)in which C is the concentration, in µg per mL, of USP Clonidine Hydrochloride RS in the Standard preparation; and rU and rS are the peak responses of clonidine hydrochloride obtained from the Assay preparation and the Standard preparation, respectively. Calculate the quantity, in mg, of chlorthalidone (C14H11ClN2O4S) in the portion of Tablets taken by the same formula, changing the terms to refer to chlorthalidone.
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USP35NF30 Page 2729