Tamoxifen Tablets

General Notices

Action and use

Selective estrogen receptor modulator.

Definition

Tamoxifen Tablets contain Tamoxifen Citrate.

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

Content of tamoxifen, C₂₆H₂₉NO

90.0 to 110.0% of the stated amount.

Identification

A. To a quantity of the powdered tablets containing the equivalent of 0.1 g of tamoxifen add 20 mL of water, warm, add 2 mL of 5m sodium hydroxide and cool. Extract with two 10-mL quantities of ether, filtering each extract in turn. Combine the ether extracts and evaporate to dryness in a current of nitrogen at room temperature. Dry the residue at a pressure not exceeding 0.7 kPa for 30 minutes. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of tamoxifen (RS 328).

B. Shake a quantity of the powdered tablets containing the equivalent of 0.1 g of tamoxifen with 10 mL of methanol, filter, evaporate the filtrate to dryness on a water bath and dry the residue at 100° for 30 minutes. Dissolve 10 mg of the dried residue in 4 mL of pyridine, add 2 mL of acetic anhydride and heat on a water bath. A rose-pink to red colour is produced.

Tests

Dissolution

Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.

test conditions

(a) Use Apparatus 1, rotating the basket at 150 revolutions per minute.

(b) Use 1000 mL of 0.02m hydrochloric acid, at a temperature of 37°, as the medium.

procedure

After 45 minutes withdraw a sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium, if necessary, at the maximum at 275 nm, Appendix II B, using 0.02m hydrochloric acid in the reference cell.

determination of content

Calculate the total content of C₂₆H₂₉NO in the medium taking 305 as the value of A(1%, 1 cm) at 275 nm.

E-Isomer and other related substances

Carry out the method for liquid chromatography, Appendix III D, protected from light and using the following solutions.

(1) To a quantity of the powdered tablets containing the equivalent of 50 mg of tamoxifen, add 35 mL of the mobile phase, mix with the aid of ultrasound for 5 minutes, dilute to 50 mL with the mobile phase, mix, centrifuge and filter the supernatant liquid through a membrane filter with a nominal pore size of 0.45 µm.

(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase.

(3) 0.15% w/v of tamoxifen citrate for performance test EPCRS in the mobile phase.

(4) Dilute 1 volume of solution (2) to 20 volumes with the mobile phase.

chromatographic conditions

(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Columbus C18 is suitable).

(b) Use isocratic elution and the mobile phase described below.

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 240 nm.

(f) Inject 20 µL of each solution.

(g) For solution (1) allow the chromatography to proceed for twice the retention time of the tamoxifen peak.

mobile phase

40 volumes of acetonitrile and 60 volumes of a mixture containing 0.09% w/v of sodium dihydrogen orthophosphate and 0.48% w/v of N,N-dimethyloctylamine, adjusted to pH 3.0 with orthophosphoric acid.

system suitability

The test is not valid unless the chromatogram obtained with solution (3) resembles that of the specimen chromatogram provided with the tamoxifen citrate for performance test EPCRS in that the resolution factor between the peaks due to the E-isomer and to tamoxifen impurity F is at least 3 and there is base-line separation of the peak due to tamoxifen impurity F from the following peak of the principal component.

limits

In the chromatogram obtained with solution (1):

the area of any peak due to the E-isomer is not greater than 0.3 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%);

the sum of the areas of all the secondary peaks, apart from any peak due to the E-isomer, is not greater than 0.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).

Disregard any peak with a retention time of less than 2.5 minutes and any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (4) (0.05%).

Assay

Weigh and powder 20 tablets. To a quantity of the powder containing the equivalent of 25 mg of tamoxifen add 100 mL of methanol, shake for 15 minutes and add sufficient methanol to produce 250 mL. Filter, dilute 10 mL of the filtrate to 100 mL with methanol and measure the absorbance of the resulting solution at 275 nm, Appendix II B. Calculate the content of C₂₆H₂₉NO taking 325 as the value of A(1%, 1 cm) at 275 nm.

Storage

Tamoxifen Tablets should be protected from light.

Labelling

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