Action and use
Oxytocic.
Definition
Ergotamine Sublingual Tablets contain Ergotamine Tartrate. They may be flavoured.
The tablets comply with the requirements stated under Oromucosal Preparations and with the following requirements.
Content of ergotamine tartrate, (C33H35N5O5)2,C4H6O6
90.0 to 105.0% 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 (5).
B. Triturate a quantity of the powdered tablets containing 2 mg of Ergotamine Tartrate with 5 mL of
petroleum spirit (boiling range, 40° to 60°), discard the petroleum spirit and triturate the residue with 10 mL of
chloroform saturated with 13.5
m ammonia. Filter and evaporate the chloroform. Dissolve 1 mg of the residue in a mixture of 5 mL of
glacial acetic acid and 5 mL of
ethyl acetate. To 1 mL of this solution add 1 mL of
sulfuric acid, with continuous shaking and cooling; a blue colour with a red tinge is produced. Add 0.1 mL of
iron(iii) chloride solution R1 previously diluted with an equal volume of
water; the red tinge becomes less apparent and the blue colour more pronounced.
Tests
Related substances
Carry out the procedure protected from light and as rapidly as possible. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in a mixture of equal volumes of dichloromethane and methanol.
(1) Extract a quantity of the powdered tablets containing 1 mg of Ergotamine Tartrate with 2 mL of a mixture of equal volumes of
dichloromethane and
methanol and centrifuge. Remove the supernatant liquid, extract the residue with two 1-mL quantities of a mixture of equal volumes of
dichloromethane and
methanol, evaporate the combined extracts to dryness at 20° at a pressure of 2 kPa and dissolve the residue in 0.25 mL of a mixture of equal volumes of
dichloromethane and
methanol. Centrifuge and use the supernatant.
(2) 0.010% w/v of ergotamine tartrate BPCRS.
(3) 0.020% w/v of ergotamine tartrate BPCRS.
(4) 0.040% w/v of ergotamine tartrate BPCRS.
(5) 0.40% w/v of ergotamine tartrate BPCRS.
chromatographic conditions
(b) Use the mobile phase as described below.
(c) Apply 5 µL of each solution.
(d) Develop the plate to 15 cm.
mobile phase
10 volumes of methanol and 90 volumes of dichloromethane.
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 (2), (3) and (4). The sum of the intensities so assessed does not exceed 10% of the intensity of the principal spot in the chromatogram obtained with solution (1). In addition, any single secondary spot in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2) (2.5%).
Uniformity of content
Tablets containing less than 2 mg and/or less than 2% w/w of Ergotamine Tartrate comply with the requirements stated under Oromucosal Preparations using the following method of analysis. Carry out the method for liquid chromatography, Appendix III D, using the following solutions in methanol (50%) containing 1% v/v of 1m hydrochloric acid.
(1) Shake one tablet with
methanol (50%) containing 1% v/v of 1
m hydrochloric acid for 15 minutes and add a sufficient volume of the same solvent to produce a solution containing 0.008% w/v of Ergotamine Tartrate and filter.
(2) 0.008% w/v of ergotamine tartrate BPCRS.
chromatographic conditions
(a) Use a stainless steel column (12.5 cm × 4.6 mm) packed with particles of silica 5 µm in diameter the surface of which has been modified with chemically bonded hexyl groups (Spherisorb C6 is suitable).
(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 detection wavelength of 210 nm.
(f) Inject 20 µL of each solution.
mobile phase
5 volumes of a 9.0% w/v solution of disodium hydrogen orthophosphate adjusted to pH 5.0 with orthophosphoric acid, 45 volumes of water and 50 volumes of methanol. The mobile phase should be adjusted to pH 3.5 with orthophosphoric acid.
determination of content
Calculate the content of (C33H35N5O5)2,C4H6O6 in each tablet using the declared content of (C33H35N5O5)2,C4H6O6 in ergotamine tartrate BPCRS.
Assay
Weigh and powder 20 tablets. Carry out the method for liquid chromatography, Appendix III D, using the following solutions in methanol (50%) containing 1% v/v of 1m hydrochloric acid.
(1) Shake a quantity of powdered tablets containing 8 mg of Ergotamine Tartrate with 50 mL of
methanol (50%) containing 1% v/v of 1
m hydrochloric acid for 15 minutes, add a sufficient volume of the same solvent to produce 100 mL and filter.
(2) 0.008% w/v of ergotamine tartrate BPCRS.
chromatographic conditions
The chromatographic procedure described under Uniformity of content may be used.
determination of content
Calculate the content of (C33H35N5O5)2,C4H6O6 using the declared content of (C33H35N5O5)2,C4H6O6 in ergotamine tartrate BPCRS.