Furosemide Tablets
Action and use
Loop diuretic.
Definition
Furosemide Tablets contain Furosemide.
Content of furosemide, C12H11ClN2O5S
95.0 to 105.0% of the stated amount.
Identification
Tests
Dissolution
Tablets containing less than 100 mg of Furosemide comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1, using Apparatus 2. Use as the medium 900 mL of phosphate buffer pH 5.8 and rotate the paddle at 50 revolutions per minute. Withdraw a sample of 10 mL of the medium, filter and dilute the filtrate with sufficient of the dissolution medium to give a solution expected to contain about 0.001% w/v of Furosemide. Measure the absorbance of this solution, Appendix II B, at 277 nm using dissolution medium in the reference cell. Calculate the total content of furosemide, C12H11ClN2O5S, in the medium from the absorbance obtained from a 0.001% w/v solution of furosemide BPCRS in the dissolution medium and using the declared content of C12H11ClN2O5S in furosemide BPCRS.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Prepare the solutions immediately before use and protect from light. For solution (1) dissolve a quantity of the powdered tablets containing 20 mg of Furosemide in sufficient of the mobile phase to produce 50 mL and mix with the aid of ultrasound for 15 minutes. For solution (2) dilute 1 volume of solution (1) to 500 volumes with the mobile phase. Solution (3) contains 0.00008% w/v of furosemide BPCRS in the mobile phase. Solution (4) contains 0.00008% w/v of each of furosemide BPCRS and furosemide impurity A EPCRS in the mobile phase. Solution (5) contains 0.00032% w/v of 4-chloro-5-sulfamoylanthranilic acid BPCRS in the mobile phase.
The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5 µm) (ChromSpher C8 is suitable), (b) as the mobile phase with a flow rate of 1 mL per minute a mixture prepared in the following manner: dissolve 0.2 g of potassium dihydrogen orthophosphate and 0.25 g of cetrimide in 70 mL of water, adjust the pH to 7.0 with 6m ammonia and add 30 mL of propan-1-ol and (c) a detection wavelength of 238 nm.
Inject 100 µL of solution (4). Adjust the sensitivity of the system so that the heights of the two peaks in the chromatogram obtained are not less than 20% of the full-scale of the recorder. The test is not valid unless the resolution factor between the first peak (furosemide impurity A) and the second peak (furosemide) is at least 4.
Inject 100 µL of solution (1) and allow the chromatography to proceed for three times the retention time of the principal peak. In the chromatogram obtained with solution (1) the area of any peak corresponding to 4-chloro-5-sulfamoylanthranilic acid is not greater than the area of the peak in the chromatogram obtained with solution (5) (0.8%) and the sum of the areas of any other secondary peaks is not greater than 2.5 times the area of the first peak in the chromatogram obtained with solution (4) (0.5%). Disregard any peak with an area less than 0.1 times the area of the first peak in the chromatogram obtained with solution (4) (0.02%).
Assay
Weigh and powder 20 tablets. Shake a quantity of the powder containing 0.2 g of Furosemide with 300 mL of 0.1m sodium hydroxide for 10 minutes, add sufficient 0.1m sodium hydroxide to produce 500 mL and filter. Dilute 5 mL to 250 mL with 0.1m sodium hydroxide and measure the absorbance of the resulting solution at the maximum at 271 nm, Appendix II B. Calculate the content of C12H11ClN2O5S taking 580 as the value of A(1%, 1 cm) at the maximum at 271 nm.