» Metolazone Tablets contain not less than 90.0% and not more than 110.0% of the labeled amount of metolazone (C16H16ClN3O3S).
Packaging and storage Preserve in tight, light-resistant containers, and store below 30.
USP Reference standards 11
Identification, Ultraviolet Absorption 197U
Solution Pipet 3 mL of the Assay preparation into a 25-mL volumetric flask, dilute with methanol to volume, and mix.
Uniformity of dosage units 905: meet the requirements.
Assay [noteUse low-actinic glassware throughout the Assay. ]
Mobile phase Dissolve 1.38 g of monobasic potassium phosphate monohydrate in about 900 mL of water, adjust with phosphoric acid to a pH of 3.0, and dilute with water to 1000 mL. Prepare a filtered and degassed mixture of this buffer solution, methanol, and acetonitrile (65:28:7). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation Dissolve an accurately weighed quantity of USP Metolazone RS in methanol to obtain a solution having a known concentration of about 5 µg per mL.
Assay preparation Transfer 10 Tablets to a 200-mL volumetric flask, and add 3 mL of water and about 100 mL of methanol. Sonicate for 30 minutes. If disintegration is not complete, sonicate for an additional 30 minutes. Shake by mechanical means for about 30 minutes. Dilute with methanol to volume, and mix. Transfer an accurately measured volume of this stock solution, equivalent to about 0.25 mg of metolazone, to a 50-mL volumetric flask, dilute with methanol to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 235-nm detector and a 3.9-mm × 15-cm column that contains packing L1. The flow rate is about 1.1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 100 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the metolazone peak. Calculate the quantity, in mg, of metolazone (C16H16ClN3O3S) in the portion of Tablets taken by the formula:
50C(rU / rS)in which C is the concentration, in mg per mL, of USP Metolazone RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 3896Pharmacopeial Forum: Volume No. 35(6) Page 1464