Ergotamine Tartrate, chemical structure, molecular formula, Reference Standards

Ergotamine Tartrate

(C33H35N5O5)2·C4H6O6 1313.41

Ergotaman-3¢,6¢,18-trione,12¢-hydroxy-2¢-methyl-5¢-(phenylmethyl)-,(5¢a)-,[R-(R*,R*)]-2,3-dihydroxybutanedioate (2:1)(salt).
Ergotamine tartrate (2:1)(salt) [379-79-3].

»Ergotamine Tartrate contains not less than 97.0percent and not more than 100.5percent of (C33H35N5O5)2·C4H6O6,calculated on the dried basis.

Packaging and storage— Preserve in well-closed,light-resistant containers in a cold place.

USP Reference standards á11ñ— USP Ergotamine Tartrate RS.

Identification— The chromatogram of the test solution prepared as directed in the test for Related alkaloidsexhibits its principal fluorescent spot and principal blue spot at the same RFvalue as the principal spot of Standard solution A.

Specific rotation á781Sñ— [NOTE—For this test,use chloroform from which any alcohol present has been removed by prior washing with water.]Dissolve about 350mg in 25mLof tartaric acid solution (1in 100)contained in a separator,then add 500mg of sodium bicarbonate,and mix gently but thoroughly.Add 10mLof chloroform,shake vigorously,and after the layers have separated draw off the chloroform phase through a small filter,previously moistened with chloroform,into a 50-mLvolumetric flask.Rapidly continue the extraction with three 10-mLportions of chloroform,passing the extracts through the same filter.Place the flask in a bath at 20

for 10minutes.Adjust the volume of extract to 50.0mLat 20

by the addition of chloroform.Mix the solution,and determine the angular rotation at 20

.Determine the concentration of ergotamine in the chloroform solution by evaporating a 25.0-mLaliquot of the solution on a rotary evaporator to dryness,maintaining the temperature of the bath below 45

.Dissolve the residue in 25mLof glacial acetic acid,add 1drop of crystal violet TS,and titrate with 0.05Nperchloric acid VSto an emerald-green endpoint.Perform a blank determination,and make any necessary correction.Each mLof 0.05Nperchloric acid is equivalent to 29.08mg of C33H35N5O5.From the angular rotation of the solution and the concentration of ergotamine base,calculate the specific rotation of the base:between -155

and -165

Loss on drying á731ñ— Dry about 100mg,accurately weighed,in vacuum at 60

for 4hours:it loses not more than 5.0%of its weight.

Related alkaloids— [NOTE—Conduct this test without exposure to daylight and with the minimum necessary exposure to artificial light.]

Solvent mixture— Mix 9volumes of chloroform with 1volume of methanol.

Standard preparation and Standard dilutions—Prepare a solution of USP Ergotamine Tartrate RSin Solvent mixtureto contain 10.0mg per mL(Standard preparation).Prepare a series of dilutions of the Standard preparationin Solvent mixtureto contain 0.2mg,0.1mg,0.05mg,and 0.025mg per mL(Standard dilutions)corresponding to 2.0%,1.0%,0.5%,and 0.25%of the Standard preparation,respectively.

Test preparation— Dissolve 50.0mg of Ergotamine Tartrate in 5.0mLof Solvent mixture.

Procedure— In a suitable chromatographic chamber arranged for thin-layer chromatography (see Chromatography á621ñ)place a volume of a solvent system consisting of ether,dimethylformamide,chloroform,and dehydrated alcohol (70:15:10:5).Line the chamber with filter paper,and allow it to equilibrate for 15minutes.Apply 5-µLportions of the Test preparation,the Standard preparation,and each of the Standard dilutionsto a suitable chromatographic plate coated with a 0.25-mm layer of chromatographic silica gel.Place each spot over an opened bottle of ammonium hydroxide for 20seconds,then allow the plate to dry in a current of cold air for 20seconds.Develop the chromatogram until the solvent front has moved about 17cm.Remove the plate from the developing chamber,allow the solvent to evaporate in a current of cold air for approximately 2minutes,and spray with a freshly prepared solution of 200mg of p-(dimethylamino)benzaldehyde in a mixture of 5.5mLof hydrochloric acid and 4.5mLof water.Dry the plate at 60

for about 5minutes and compare the chromatograms:the RFvalue of the principal spot obtained from the Test preparationcorresponds to that obtained from the Standard preparation,the sum of the intensities of any secondary spots in the chromatogram from the Test preparationis not greater than the intensity of the principal spot from the 2.0%Standard dilution,and the intensity of not more than one of the secondary spots is greater than that of the principal spot from the 1.0%Standard dilution.

Assay— Transfer about 200mg of Ergotamine Tartrate,accurately weighed,to a small conical flask,and dissolve in 15mLof a mixture of 6volumes of acetic anhydride and 100volumes of glacial acetic acid.Add 1drop of crystal violet TS,and titrate with 0.05Nperchloric acid VSfrom a 10-mLburet.Perform a blank determination,and make any necessary correction.Each mLof 0.05Nperchloric acid is equivalent to 32.84mg of (C33H35N5O5)2·C4H6O6.

Auxiliary Information— Staff Liaison:Ravi Ravichandran,Ph.D.,Senior Scientist

Expert Committee:(PA3)Pharmaceutical Analysis 3

USP28–NF23Page 753

Pharmacopeial Forum:Volume No.29(6)Page 1884

Phone Number:1-301-816-8330