Loss on drying 
731
—
Dry about 2 g, accurately weighed, at 105
for 4 hours: it loses not more than 0.4% of its weight.
Limit of 4¢-chloro-3¢-sulfamoyl-2-benzophenone carboxylic acid (CCA)—
Proceed as directed in the
Assay, except to calculate the quantity, in mg, of CCA in the portion of Chlorthalidone taken by the formula:
(0.5)C(RU / RS),
in which
C is the concentration, in µg per mL, of
USP 4¢-Chloro-3¢-sulfamoyl-2-benzophenone Carboxylic Acid RS in the
Standard preparation; and
RU and
RS are the peak response ratios of CCA and the internal standard obtained from the
Assay preparation and the
Standard preparation, respectively: not more than 1.0% is present.
Assay—
Mobile phase—
Prepare a suitable degassed mixture of 0.01 M dibasic ammonium phosphate and methanol (3:2), adjust dropwise with phosphoric acid to a pH of 5.5 ± 0.1, and filter.
Internal standard solution—
Prepare a solution of 2,7-naphthalenediol in methanol having a concentration of about 1.0 mg per mL.
Standard preparation—
Prepare a solution of
USP Chlorthalidone RS in methanol having a known concentration of about 1 mg per mL. Pipet 5 mL of this solution into a 50-mL volumetric flask containing 5.0 mL of
Internal standard solution and 10.0 mL of CCA solution. Dilute with water to volume, and mix.
Assay preparation—
Transfer about 50 mg of Chlorthalidone, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with methanol to volume, and mix. Pipet 5 mL of this solution into a 50-mL volumetric flask containing 5.0 mL of Internal standard solution and 10.0 mL of methanol. Dilute with water 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 L7. The flow rate is about 1.0 mL per minute. Chromatograph five replicate injections of the
Standard preparation, and record the peak responses as directed for
Procedure: the relative standard deviation is not more than 2.0%, and the resolution factors between Chlorthalidone and CCA, and between chlorthalidone and the internal standard, are not less than 1.5. The tailing factors for the Chlorthalidone and CCA peaks are not more than 2.0.
Procedure—
Separately inject equal volumes (about 25 µL) of the
Standard preparation and the
Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The relative retention times are about 0.5 for CCA, 0.8 for Chlorthalidone and 1.0 for the internal standard. Calculate the quantity, in mg, of C
14H
11ClN
2O
4S in the portion of Chlorthalidone taken by the formula:
500C(RU / RS),
in which
C is the concentration, in mg per mL, of
USP Chlorthalidone RS in the
Standard preparation; and
RU and
RS are the peak response ratios of chlorthalidone and the internal standard obtained from the
Assay preparation and the
Standard preparation, respectively.
;)
