Ergotamine Tartrate Tablets
»Ergotamine Tartrate Tablets contain not less than 90.0percent and not more than 110.0percent of the labeled amount of (C33H35N5O5)2·C4H6O6.
Packaging and storage— Preserve in well-closed,light-resistant containers.
Labeling— Label the Tablets to indicate whether they are intended for sublingual administration or for swallowing.
Identification— Triturate a quantity of finely powdered Tablets,equivalent to about 5mg of ergotamine tartrate,with 10mLof solvent hexane for a few minutes,allow to settle,and discard the solvent hexane extract.Add to the residue 10mLof chloroform saturated with ammonia (prepared by shaking chloroform with ammonium hydroxide,then drawing off the chloroform layer),triturate for a few minutes,filter,and evaporate the filtrate on a steam bath to dryness.Dissolve the residue in a mixture of 4mLof glacial acetic acid and 4mLof ethyl acetate.To 1mLof this solution add slowly,with continuous agitation and cooling,1mLof sulfuric acid:a blue color with a red tinge develops.Add 0.1mLof ferric chloride TS,previously diluted with an equal volume of water:the red tinge becomes less apparent and the blue color more pronounced.
Disintegration á701ñ(for Tablets intended for sublingual use): 5minutes.
Dissolution á711ñ(for Tablets intended to be swallowed)—
Medium: tartaric acid solution (1in 100);1000mL.
Apparatus 2: 75rpm.
Time: 30minutes.
Procedure— Determine the amount of (C33H35N2O5)2·C4H6O6dissolved from fluorescence intensities,using the maximum excitation wavelength at about 327nm and the maximum emission wavelength at about 427nm,of filtered portions of the solution under test,suitably diluted with Dissolution Medium,if necessary,in comparison with a Standard solution having a known concentration of USP Ergotamine Tartrate RSin the same Medium.
Tolerances— Not less than 75%(Q)of the labeled amount of (C33H35N2O5)2·C4H6O6is dissolved in 30minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Assay—
Mobile phase— Prepare a filtered and degassed mixture of acetonitrile and 0.01Mmonobasic potassium phosphate (55:45).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ.
Internal standard solution— Transfer about 40mg of ergonovine maleate to a 250-mLvolumetric flask,add a mixture of acetonitrile and water (55:45)to volume,and mix.
Standard preparation— Transfer about 10mg of USP Ergotamine Tartrate RS,accurately weighed,to a 50-mLvolumetric flask,add a mixture of acetonitrile and water (55:45)to volume,and mix.Transfer 5.0mLof this solution to a 50-mLvolumetric flask,add 5.0mLof Internal standard solution,dilute with the mixture of acetonitrile and water (55:45)to volume,and mix to obtain a solution having a known concentration of about 0.02mg of USP Ergotamine Tartrate RSper mL.
Assay preparation— Transfer a number of whole Tablets,equivalent to about 10mg of ergotamine tartrate,to a 500-mLvolumetric flask.Add 50.0mLof Internal standard solution,300mLof a mixture of acetonitrile and water (55:45),and sonicate for about 10minutes.Dilute with the mixture of acetonitrile and water (55:45)to volume,and mix.Filter through a 0.45-µm membrane disk,discarding the first 25mLof the filtrate.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the resolution,R,between the analyte and internal standard peaks is not less than 3.0;the column efficiency determined from the analyte peak is not less than 3000theoretical plates;the tailing factor for the analyte peak is not more than 2.0;and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.The relative retention times are about 0.7for ergonovine maleate and 1.0for ergotamine tartrate.Calculate the quantity,in mg,of (C33H35N5O5)2·C4H6O6in the portion of Ergotamine Tartrate Tablets taken by the formula:
500C(RU/RS),
in which Cis the concentration,in mg per mL,of USP Ergotamine Tartrate RSin the Standard preparation,and RUand RSare the peak response ratios obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Ravi Ravichandran,Ph.D.,Senior Scientist
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 755
Pharmacopeial Forum:Volume No.30(4)Page 1198
Phone Number:1-301-816-8330