Fludrocortisone Tablets

General Notices

Action and use

Mineralocorticoid.

Definition

Fludrocortisone Tablets contain Fludrocortisone Acetate.

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

Content of fludrocortisone acetate, C23H31FO6

90.0 to 110.0% of the stated amount.

Identification

A. Complies with the test for identification of steroids, Appendix III A, using impregnating solvent I and mobile phase B. Apply separately to the plate 20 µL of each of the following solutions. For solution (1) shake a quantity of the powdered tablets containing 1 mg of fludrocortisone acetate with 20 mL of chloroform for 5 minutes, filter, evaporate the filtrate to dryness and dissolve the residue in 4 mL of a mixture of 9 volumes of chloroform and 1 volume of methanol. Solution (2) contains 0.025% w/v of fludrocortisone acetate BPCRS in a mixture of 9 volumes of chloroform and 1 volume of methanol.
B. In the Assay, the chromatogram obtained with solution (1) shows a peak with the same retention time as the peak due to fludrocortisone acetate in the chromatogram obtained with solution (2).

Tests

Uniformity of content

Tablets containing less than 2 mg and/or less than 2% w/w of Fludrocortisone Acetate comply with the requirement stated under Tablets using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions protected from light. Solution A contains 0.002% w/v of norethisterone BPCRS in acetonitrile.

(1) Place a single tablet in a centrifuge tube, add 1 mL of water, shake on a vortex-type mixer for 1 minute, add 4.0 mL of solution A and shake again for 1 minute. Shake for a further 40 minutes on a mechanical shaker, centrifuge and use the clear supernatant solution.
(2) 4 volumes of a 0.0025% w/v solution of fludrocortisone acetate BPCRS in solution A and 1 volume of water.
chromatographic conditions
(a) Use a stainless steel column (20 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (10 µm) (Spherisorb ODS 1 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 240 nm.
(f) Inject 20 µL of each solution.
mobile phase

40 volumes of acetonitrile and 60 volumes of water.

determination of content

Calculate the content of C23H31FO6 in each tablet using the declared content of C23H31FO6 in fludrocortisone acetate BPCRS.

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Solution A contains 0.01% w/v of norethisterone BPCRS (internal standard) in acetonitrile.

(1) Shake a quantity of the powdered tablets containing 0.5 mg of fludrocortisone acetate with 2 mL of water for 1 minute, add 4 mL of solution A and 4 mL of acetonitrile and shake on a mechanical shaker for 40 minutes. Dilute the mixture to 20 mL with acetonitrile, centrifuge and use the supernatant liquid.
(2) 20 mL of solution A, 25 mL of a 0.01% w/v solution of fludrocortisone acetate BPCRS in acetonitrile and 10 mL of water diluted to 100 mL with acetonitrile.
(3) Prepare in the same manner as solution (1) but using 8 mL of acetonitrile in place of 4 mL of solution A and 4 mL of acetonitrile.
chromatographic conditions
The chromatographic conditions described under Uniformity of content may be used.
determination of content

Calculate the content of C23H31FO6 in the tablets using the declared content of C23H31FO6 in fludrocortisone acetate BPCRS.