Ethacrynic Acid Tablets

» Ethacrynic Acid Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of ethacrynic acid (C13H12Cl2O4).

Packaging and storage— Preserve in well-closed containers.

—

USP Ethacrynic Acid RS

Identification—

A: Weigh a portion of finely powdered Tablets, equivalent to about 50 mg of ethacrynic acid, and transfer to a separator containing 25 mL of 0.1 N hydrochloric acid. Extract with two 40-mL portions of methylene chloride, filter the extracts into a 100-mL volumetric flask, and dilute with methylene chloride to volume. Transfer 10.0 mL of this solution to a 100-mL volumetric flask, evaporate in a gentle current of air to dryness, and promptly dissolve the residue in a portion of a 9 in 1000 mixture of hydrochloric acid in anhydrous methanol, then dilute with the acidic methanol to volume: the UV absorption spectrum of the solution exhibits maxima and minima at the same wavelengths as that of a solution of USP Ethacrynic Acid RS in the acidic methanol containing 50 µg per mL, concomitantly measured.

B: A portion of powdered Tablets, equivalent to 25 mg of ethacrynic acid, responds to Identification test C under Ethacrynic Acid.

Dissolution

711

—

Medium: 0.1 M phosphate buffer, prepared by mixing 13.6 g of monobasic potassium phosphate and 92.2 mL of 1 N sodium hydroxide with water to obtain 1000 mL of a solution having a pH of 8.0 ± 0.05; 900 mL.

Apparatus 2: 50 rpm.

Time: 45 minutes.

Procedure— Determine the amount of C13H12Cl2O4 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 277 nm on filtered portions of the solution under test, suitably diluted with Medium, in comparison with a Standard solution having a known concentration of USP Ethacrynic Acid RS in the same Medium.

Tolerances— Not less than 75% (Q) of the labeled amount of C13H12Cl2O4 is dissolved in 45 minutes.

Uniformity of dosage units

905

: meet the requirements.

Procedure for content uniformity— Add 1 Tablet to a 100-mL volumetric flask containing 10 mL of water, and allow to stand for 15 minutes, shaking occasionally until the tablet is disintegrated. Add a 9 in 1000 mixture of hydrochloric acid in methanol to volume, and mix. Filter a portion of the mixture, and pipet a volume of the filtrate, equivalent to 5 mg of ethacrynic acid, into a 100-mL volumetric flask. Dilute with the acidic methanol to volume, and mix. Dissolve an accurately weighed quantity of USP Ethacrynic Acid RS in the acidic methanol, and dilute quantitatively and stepwise with the same solvent to obtain a Standard solution having a known concentration of about 50 µg per mL. Concomitantly determine the absorbances of both solutions in 1-cm cells at the wavelength of maximum absorbance at about 269 nm, with a suitable spectrophotometer, using the acidic methanol as the blank. Calculate the quantity, in mg, of C13H12Cl2O4 in the Tablet by the formula:

(T / D)C(AU / AS)

in which T is the labeled quantity, in mg, of ethacrynic acid in the Tablet; D is the concentration, in µg per mL, of ethacrynic acid in the solution from the Tablet, on the basis of the labeled quantity per Tablet and the extent of dilution; C is the concentration, in µg per mL, of USP Ethacrynic Acid RS in the Standard solution; and AU and AS are the absorbances of the solution from the Tablet and the Standard solution, respectively.

Assay—

Triethylamine solution— Mix 10 mL of triethylamine and about 900 mL of water in a 1-L volumetric flask. Adjust with phosphoric acid to a pH of 6.8 ± 0.1, dilute with water to volume, mix, and filter.

Solvent mixture— Prepare a mixture of water and acetonitrile (3:2).

Mobile phase— Prepare a filtered and degassed mixture of Triethylamine solution and acetonitrile (3:2). Make adjustments if necessary (see System Suitability under Chromatography

621

Standard preparation— Dissolve an accurately weighed quantity of USP Ethacrynic Acid RS in Solvent mixture, and dilute quantitatively with Solvent mixture, to obtain a solution having a known concentration of about 0.5 mg per mL.

Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 50 mg of ethacrynic acid, to a 100-mL volumetric flask, add about 80 mL of Solvent mixture, and shake or sonicate to dissolve the ethacrynic acid. Dilute with Solvent mixture to volume, and mix.

Chromatographic system (see Chromatography

621

)—The liquid chromatograph is equipped with a 254-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 column efficiency determined from the analyte peak is not less than 1200 theoretical plates; the tailing factor for the analyte peak is not more than 2; the capacity factor, k¢, is not less than 0.8; and the relative standard deviation for replicate injections is not more than 1.0.%.

Procedure— Separately inject equal volumes (about 10 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 ethacrynic acid (C13H12Cl2O4) in the portion of Tablets taken by the formula:

100C(rU / rS)

in which C is the concentration, in mg per mL, of USP Ethacrynic Acid RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Sujatha Ramakrishna, Ph.D. Senior Scientific Liaison 1-301-816-8349	(SM22010) Monographs - Small Molecules 2
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org
711	Margareth R.C. Marques, Ph.D. Senior Scientific Liaison 1-301-816-8106	(GCDF2010) General Chapters - Dosage Forms

USP35–NF30 Page 3122

Pharmacopeial Forum: Volume No. 30(6) Page 1993