Sumatriptan Tablets

General Notices

Action and use

Serotonin 5HT1 receptor agonist; treatment of migraine.

Definition

Sumatriptan Tablets contain Sumatriptan Succinate.

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

Content of sumatriptan, C14H21N3O2S

95.0 to 105.0% of the stated amount.

Identification

Add 10 mL of methanol to a quantity of powdered tablets containing the equivalent of 70 mg of sumatriptan, mix with the aid of ultrasound for 5 minutes, filter through a 0.45-µm PTFE filter, evaporate the filtrate and dry under reduced pressure for 1 hour. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of sumatriptan succinate (RS 413).

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 15 minutes withdraw a sample of the medium and measure the absorbance of the filtered sample, suitably diluted with the dissolution medium if necessary, to give a solution expected to contain the equivalent of 0.0011% w/v of sumatriptan, at the maximum at 282 nm, Appendix II B using water in the reference cell.
(2) Measure the absorbance, of 0.0013% w/v solution of sumatriptan succinate BPCRS in water using water in the reference cell.
determination of content

Calculate the total content of C14H21N3O2S, in the medium from the absorbances obtained and using the declared content of C14H21N3O2S,C4H6O4 in sumatriptan succinate BPCRS. 1 mg of C14H21N3O2S,C4H6O4 is equivalent to 0.714 mg of C14H21N3O2S.

Impurities A and H

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

(1) Add 100 mL of 0.1m hydrochloric acid to a quantity of the powdered tablets containing the equivalent of 0.14 g of sumatriptan, mix with the aid of ultrasound and filter through a 0.45-µm PTFE filter.
(2) Dilute 1 volume of solution (1) to 100 volumes with 0.1m hydrochloric acid and dilute 3 volumes of the resulting solution to 4 volumes with the same solvent.
(3) Dilute the contents of a vial of sumatriptan for system suitability EPCRS to 1 mL with 0.1m hydrochloric acid.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with silica gel for chromatography (Spherisorb silica S5W is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 282 nm.
(f) Inject 20 µL of each solution.
(g) For solution (1) allow the chromatography to proceed for 5 times the retention time of the principal peak.
mobile phase

10 volumes of 10m ammonium acetate and 90 volumes of methanol.

system suitability

The test is not valid unless, using solution (3):

the chromatogram resembles that supplied with sumatriptan for system suitability EPCRS;

the resolution between impurity A and sumatriptan is at least 1.5.

limits

Identify any peak in the chromatogram obtained with solution (1) due to impurity A using the chromatogram obtained with solution (3). Multiply the area of any peak corresponding to impurity A by a correction factor of 0.5.

In the chromatogram obtained with solution (1):

the area of any peak corresponding to impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.75%);

the area of any peak corresponding to impurity H is not greater than 0.4 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%).

Related substances

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

(1) Add 100 mL of 0.1m hydrochloric acid to a quantity of the powdered tablets containing the equivalent of 0.14 g of sumatriptan, mix with the aid of ultrasound and filter through a 0.45-µm PTFE filter.
(2) Dilute 3 volumes of solution (1) to 100 volumes with 0.1m hydrochloric acid and dilute 1 volume of the resulting solution to 10 volumes with 0.1m hydrochloric acid.
(3) Dilute the contents of a vial of sumatriptan impurity mixture EPCRS to 1 mL with 0.1m hydrochloric acid.
chromatographic conditions
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS 1 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 282 nm.
(f) Inject 20 µL of each solution.
(g) For solution (1) allow the chromatography to proceed for 4 times the retention time of the principal peak.
mobile phase

25 volumes of acetonitrile and 75 volumes of a solution containing 0.97 g of dibutylamine, 0.735 g of orthophosphoric acid and 2.93 g of sodium dihydrogen orthophosphate in 750 mL of water, adjusted to pH 7.5 with 10m sodium hydroxide and diluted to 1000 mL with water.

system suitability

The test is not valid unless in solution (3):

the chromatogram resembles that supplied with sumatriptan impurity mixture EPCRS;

the resolution between impurity C and sumatriptan is at least 1.5.

limits

In the chromatogram obtained with solution (1):

the area of any peaks corresponding to impurities B, C or D is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.75%);

the area of any other secondary peak is not greater than area of the principal peak in the chromatogram obtained with solution (2) (0.3%).

Disregard any peak with an area less than a third of the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).

The total impurity content in the test for Impurities A and H and the test for Related substances is not greater than 2.0%.

Assay

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

(1) Add 100 mL of 0.1m hydrochloric acid to a quantity of the powdered tablets containing the equivalent of 0.1429 g of sumatriptan, mix with the aid of ultrasound, filter through a 0.45-µm PTFE filter and dilute 1 volume to 10 volumes with 0.1m hydrochloric acid.
(2) 0.02% w/v of sumatriptan succinate BPCRS in 0.1m hydrochloric acid.
(3) Dilute the contents of a vial of sumatriptan impurity mixture EPCRS to 1 mL with 0.1 m hydrochloric acid.
chromatographic conditions

The chromatographic procedure described under Related substances may be used.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between sumatriptan and impurity C is at least 1.5.

determination of content

Calculate the content of C14H21N3O2S in the tablets using the declared content of C14H21N3O2S,C4H6O4 in sumatriptan succinate BPCRS. 1 mg of C14H21N3O2S,C4H6O4 is equivalent to 0.714 mg of C14H21N3O2S.

Labelling

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

Impurities

The impurities limited by the requirements of this monograph include those listed under Sumatriptan Succinate.