Estramustine Phosphate Capsules

General Notices

Action and use

Cytotoxic alkylating agent.

Definition

Estramustine Phosphate Capsules contain Estramustine Sodium Phosphate.

The capsules comply with the requirements stated under Capsules and with the following requirements.

Content of estramustine phosphate, C23H32Cl2NO6P

92.5 to 107.5% of the stated amount.

Identification

A. Shake a quantity of the contents of the capsules containing the equivalent of 0.2 g of Estramustine Phosphate with 10 mL of methanol, filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of estramustine sodium phosphate (RS 128). In preparing the potassium bromide disc precautions should be taken to exclude moisture and avoid excessive grinding; if necessary heat the prepared disc at 90° for 2 minutes.
B. A 1% w/v solution of the residue obtained in test A yields the reactions characteristic of sodium salts, Appendix VI.

Tests

Related substances

Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in a mixture of 1 volume of triethylamine and 49 volumes of methanol.

(1) 4.0% w/v of the residue obtained in test A for Identification.
(2) 0.020% w/v of the residue obtained in test A for Identification.
(3) 0.080% w/v of 17β,17′β-bis{3-[bis(2-chloroethyl)carbamoyloxy]estra1,3,5(10)-trienyl} pyrophosphate BPCRS.
(4) 0.040% of estramustine BPCRS.
chromatographic conditions
(a) Use as the coating silica gel.
(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, dry in air, spray with methanolic sulfuric acid (20%) and heat at 110° for 10 minutes.
mobile phase

Equal volumes of butan-2-one, propan-2-ol and triethylamine hydrogen carbonate solution.

limits

In the chromatogram obtained with solution (1):

any secondary spot due to 17β,17′β-bis{3-[bis(2-chloroethyl)carbamoyloxy]estra1,3,5(10)-trienyl} pyrophosphate is not more intense than the corresponding spot in the chromatogram obtained with solution (3) (2%);

any secondary spot due to estramustine is not more intense than the corresponding spot in the chromatogram obtained with solution (4) (1%);

Any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%).

Assay

Shake a quantity of the mixed contents of 20 capsules containing the equivalent of 0.28 g of Estramustine Phosphate with 20 mL of water, dilute to 50 mL with water and filter. Dilute 5 mL of the filtrate to 100 mL with ethanol (50%) and measure the absorbance of the resulting solution at the maximum at 275 nm, Appendix II B. Calculate the content of C23H32Cl2NO6P taking 15.4 as the value of A (1%, 1 cm) at the maximum at 275 nm.

Labelling

The quantity of active ingredient is stated in terms of the equivalent amount of estramustine phosphate.