Action and use
Non-selective 5HT receptor antagonist.
Definition
Methysergide Tablets contain Methysergide Maleate. They are coated.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of methysergide, C21H27N3O2
90.0 to 110.0% of the stated amount.
Identification
A. In the test for Related substances, the principal spot in the chromatogram obtained with solution (1) corresponds to that in the chromatogram obtained with solution (8).
Tests
Dissolution
Carry out the following procedure protected from light. The tablets 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 120 revolutions per minute.
procedure
Carry out the method for liquid chromatography, Appendix III D, using the following solutions protected from light.
(1) After 45 minutes withdraw a 20 mL sample of the medium and filter through a membrane filter having a nominal pore size not greater than 0.45 µm, discarding the first 10 mL of filtrate.
chromatographic conditions
(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 fluorimetric detector with an excitation wavelength of 325 nm and an emission wavelength of 430 nm.
(f) Inject 20 µL of each solution.
mobile phase
35 volumes of acetonitrile and 65 volumes of 0.01m diammonium hydrogen orthophosphate.
determination of content
Calculate the total content of methysergide, C21H27N3O2, in the medium using the declared content of C21H27N3O2 in methysergide maleate BPCRS.
Related substances
Carry out in subdued light the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Place a quantity of the powdered tablets containing the equivalent of 5.0 mg of methysergide in a sintered-glass filter, add 10 mL of
petroleum spirit (boiling range, 40° to 60°), stir for 2 minutes and filter. Repeat the washing with two further 10 mL quantities of the petroleum spirit and discard the washings. Extract with four 20 mL quantities of a solution prepared by shaking 100 mL of
chloroform vigorously with 0.15 mL of 13.5
m ammonia. Evaporate the filtrate to dryness at room temperature at a pressure of 2 kPa and dissolve the residue in 1 mL of a mixture of 1 volume of 13.5
m ammonia and 100 volumes of
methanol.
(2) Dissolve 14 mg of
methysergide maleate BPCRS in a mixture of 1 mL of
ethanol (96%) and 19 mL of a 1% w/v solution of
(+)-tartaric acid. Make alkaline by the addition of 0.15 mL of 13.5
m ammonia and extract with successive quantities of 20, 10, 10 and 10 mL of
chloroform. Filter the combined extracts and evaporate to dryness at room temperature at a pressure of 2 kPa. Dissolve the residue in 2 mL of a mixture of 1 volume of 13.5
m ammonia and 100 volumes of
methanol.
(3) 0.0025% w/v of methysergide, prepared by diluting solution (2) with a mixture of 1 volume of 13.5
m ammonia and 100 volumes of
methanol.
(4) 0.005% w/v of methysergide, prepared by diluting solution (2) with a mixture of 1 volume of 13.5
m ammonia and 100 volumes of
methanol.
(5) 0.01% w/v of methysergide, prepared by diluting solution (2) with a mixture of 1 volume of 13.5
m ammonia and 100 volumes of
methanol.
(6) 0.015% w/v of methysergide, prepared by diluting solution (2) with a mixture of 1 volume of 13.5
m ammonia and 100 volumes of
methanol.
(7) 0.02% w/v of methysergide, prepared by diluting solution (2) with a mixture of 1 volume of 13.5
m ammonia and 100 volumes of
methanol.
(8) 0.025% w/v of methysergide, prepared by diluting solution (2) with a mixture of 1 volume of 13.5
m ammonia and 100 volumes of
methanol.
chromatographic conditions
(b) Use the mobile phase as described below.
(c) Apply 10 µL of each solution.
(d) Develop the plate to 15 cm.
mobile phase
10 volumes of methanol and 90 volumes of chloroform.
limits
Assess the intensities of any secondary spots in the chromatogram obtained with solution (1) by reference to the spots in the chromatograms obtained with solutions (3) to (8), making allowance for area in assessing the intensities of spots with different Rf values and disregarding any spots less intense than the spot in the chromatogram obtained with solution (3). The sum of the intensities so assessed does not exceed 5% of the intensity of the principal spot in the chromatogram obtained with solution (1).
Uniformity of content
Tablets containing less than the equivalent of 2 mg and/or less than 2% w/w of methysergide comply with the requirements stated under Tablets using the following method of analysis protected from light. To one tablet add 50 mL of a 1% w/v solution of (+)-tartaric acid, shake for 30 minutes and centrifuge. Measure the absorbance of the supernatant liquid at the maximum at 322 nm, Appendix II B. Calculate the content of C21H27N3O2 taking 227 as the value of A(1%, 1 cm) at the maximum at 322 nm.
Assay
Carry out the following procedure protected from light. Weigh and powder 20 tablets. To a quantity of the powder containing the equivalent of 20 mg of methysergide add 50 mL of a 1% w/v solution of (+)-tartaric acid and 0.2 mL of a 20% w/v solution of benzalkonium chloride and shake for 30 minutes. Dilute with the tartaric acid solution to 100 mL, mix and filter, discarding the first few mL. To 10 mL of the filtrate add sufficient of the tartaric acid solution to produce 100 mL and measure the absorbance at the maximum at 322 nm, Appendix II B. Calculate the content of C21H27N3O2 taking 227 as the value of A(1%, 1 cm) at the maximum at 322 nm.
Storage
Methysergide Tablets should be protected from light.
Labelling
The quantity of active ingredient is stated in terms of the equivalent amount of methysergide.