Tioguanine Tablets

General Notices

Action and use

Purine analogue; cytostatic.

Definition

Tioguanine Tablets contain Tioguanine.

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

Content of tioguanine, C₅H₅N₅S

92.5 to 105.0% of the stated amount.

Identification

Shake a quantity of the powdered tablets containing 0.5 g of Tioguanine with 10 mL of 1m sodium hydroxide and filter. Acidify the filtrate with hydrochloric acid, filter, dissolve the precipitate in 13.5m ammonia, evaporate to dryness and dry the residue at 105° at a pressure not exceeding 0.7 kPa for 5 hours. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of tioguanine (RS 340).

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 2, rotating the paddle at 50 revolutions per minute.

(b) Use 900 mL of water at a temperature of 37°, as the medium.

procedure

(1) After 45 minutes withdraw 10 mL of the medium and filter. To 2 mL of the filtrate add 2 mL of 1m hydrochloric acid and dilute to 20 mL with water. Measure the absorbance of the solution at the maximum at 348 nm, Appendix II B, using 0.1m hydrochloric acid in the reference cell.

(2) Measure the absorbance of a suitable solution of tioguanine BPCRS using 0.1m hydrochloric acid in the reference cell.

determination of content

Calculate the total content of tioguanine, C₅H₅N₅S, in the medium from the absorbances obtained and using the declared content of C₅H₅N₅S in tioguanine BPCRS.

Related substances

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

(1) Disperse a quantity of the powdered tablets containing 40 mg of Tioguanine in 100 mL of0.01m sodium hydroxide with the aid of ultrasound for 5 minutes. Mix and filter. Dilute 1 volume of the filtrate to 2 volumes with mobile phase.

(2) Dilute 1 volume of solution (1) to 100 volumes with a mixture of 1 volume of 0.01m sodium hydroxide and 9 volumes of mobile phase. Further dilute 1 volume of this solution to 5 volumes with the same solvent mixture.

(3) Dissolve 16 mg of guanine BPCRS in 100 mL of 0.01m sodium hydroxide and dilute 1 volume of the resulting solution to 20 volumes with the mobile phase.

(4) Dissolve 40 mg each of tioguanine BPCRS and guanine BPCRS in 100 mL of 0.01m sodium hydroxide and dilute 1 volume of this solution to 10 volumes with the mobile phase.

chromatographic conditions

(a) Use a stainless steel column (5 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Waters Atlantis dC18 is suitable).

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

(d) Use an ambient column temperature.

(e) Use a detection wavelength of 248 nm.

(f) Inject 10 µL of each solution.

mobile phase

0.05m anhydrous sodium dihydrogen orthophosphate adjusted to pH 3.0 with orthophosphoric acid (85%).

system suitability

The test is not valid unless, in the chromatogram obtained with solution (4), the resolution factor between the peaks due to tioguanine and guanine is at least 3.0.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to guanine is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (4%);

the area of any other secondary peak is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);

the sum of the areas of any other secondary peaks is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).

Disregard any peak with an area less than 0.25 times the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).

Assay

Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions.

(1) To a quantity of the powdered tablets containing 40 mg of Tioguanine add 70 mL of 0.01m sodium hydroxide, shake for 15 minutes and dilute to 100 mL with the same solvent. Filter and dilute 1 volume of the resulting solution to 10 volumes with the mobile phase.

(2) Dissolve 40 mg of tioguanine BPCRS in 100 mL of 0.01m sodium hydroxide and dilute 1 volume of the resulting solution to 10 volumes with the mobile phase.

(3) Dissolve 40 mg each of tioguanine BPCRS and guanine BPCRS in 100 mL of 0.01m sodium hydroxide and dilute 1 volume of the resulting solution to 10 volumes with the mobile phase.