Bumetanide Tablets

General Notices

Action and use

Loop diuretic.

Definition

Bumetanide Tablets contain Bumetanide.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of bumetanide, C17H20N2O5S

95.0 to 105.0% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing 50 mg of Bumetanide with 25 mL of ether, filter through anhydrous sodium sulfate and evaporate the filtrate to dryness using a rotary evaporator. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of bumetanide (RS 033).
B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the peak in the chromatogram obtained with solution (2).

Tests

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.

(1) Shake mechanically a quantity of the powdered tablets containing 12.5 mg of Bumetanide with 20 mL of a mixture of equal volumes of acetonitrile and methanol for 20 minutes, centrifuge for 10 minutes, decant and reserve the supernatant liquid. Extract the residue with 5 mL of a mixture of equal volumes of acetonitrile and methanol, shaking mechanically for 30 seconds, centrifuge for 10 minutes, decant and combine the extracts. Evaporate the combined extracts to dryness under reduced pressure, dissolve the residue in 0.5 mL of methanol and centrifuge for 10 minutes.
(2) Dilute 1 volume of solution (1) to 100 volumes with methanol and further dilute 3 volumes of this solution to 10 volumes with methanol.
(3) Dilute 1 volume of solution (1) to 10 volumes with methanol and further dilute 1 volume of this solution to 100 volumes with methanol.
chromatographic conditions
(a) Use a precoated TLC silica gel F254 plate (Merck silica gel 60 F254 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm).
mobile phase

2.5 volumes of methanol, 10 volumes of glacial acetic acid, 10 volumes of cyclohexane and 80 volumes of chloroform.

limits

Any secondary spot in the chromatogram obtained with solution (1):

is not more intense than the spot in the chromatogram obtained with solution (2) (0.3%);

and not more than three such spots are more intense than the spot in the chromatogram obtained with solution (3) (0.1%).

Uniformity of content

Tablets containing less than 2 mg and/or less than 2% w/w of Bumetanide comply with the requirements stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Dissolve one tablet in 10 mL of a mixture of 2 volumes of glacial acetic acid, 5 volumes of tetrahydrofuran and 45 volumes of methanol, shake with the aid of ultrasound for 5 minutes, dilute to 20 mL with water, filter and use the filtrate.
(2) Dilute 10 mL of a 0.010% w/v solution of bumetanide BPCRS in a mixture of 2 volumes of glacial acetic acid, 5 volumes of tetrahydrofuran and 45 volumes of methanol to 20 mL with water.
Chromatographic Conditions

The chromatographic procedure described under Assay may be used.

Determination of Content

Calculate the content of C17H20N2O5S in each tablet using the declared content of C17H20N2O5S in bumetanide BPCRS.

Assay

Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) Dissolve a quantity of the powdered tablets containing 2.5 mg of Bumetanide in 10 mL of a mixture of 2 volumes of glacial acetic acid, 5 volumes of tetrahydrofuran and 45 volumes of methanol, shake with the aid of ultrasound for 5 minutes, dilute to 20 mL with water, filter and use the filtrate.
(2) Dilute 10 mL of a 0.025% w/v solution of bumetanide BPCRS in a mixture of 2 volumes of glacial acetic acid, 5 volumes of tetrahydrofuran and 45 volumes of methanol to 20 mL with water.
(3) 0.0125% w/v of 3-amino-4-phenoxy-5-sulfamoylbenzoic acid BPCRS in solution (2).
chromatographic conditions
(a) Use a stainless steel column (30 cm × 3.9 mm) packed with end-capped octadecylsilyl silica gel for chromatography (10 µm) (µBondapak ODS is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
mobile phase

2 volumes of glacial acetic acid, 5 volumes of tetrahydrofuran, 45 volumes of water and 50 volumes of methanol.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the two principal peaks is at least 15.

determination of content

Calculate the content of C17H20N2O5S in the tablets using the declared content of C17H20N2O5S in bumetanide BPCRS.