Ergoloid Mesylates
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C35H41N5O5·CH4O3S(dihydroergocristine mesylate)
707.84
C32H43N5O5·CH4O3S(dihydro-a-ergocryptine mesylate)
673.82
C32H43N5O5·CH4O3S(dihydro-b-ergocryptine mesylate)
673.82
Ergotaman-3¢,6¢,18-trione,9,10-dihydro-12¢-hydroxy-2¢,5¢-bis(1-methylethyl)-,(5¢a,10a)-,monomethanesulfonate (salt)mixture with 9,10a-dihydro-12¢-hydroxy-2¢-(1-methylethyl)-5¢a-(phenylmethyl)ergotaman-3¢,6¢,18-trione monomethanesulfonate (salt),9,10a-dihydro-12¢-hydroxy-2¢-(1-methylethyl)-5¢a-(2-methylpropyl)ergotaman-3¢,6¢,18-trione monomethanesulfonate (salt),and 9,10a-dihydro-12¢-hydroxy-2¢-(1-methylethyl)-5¢a-(1-methylpropyl)ergotaman-3¢,6¢,18-trione monomethanesulfonate (salt).
Dihydroergotoxine monomethanesulfonate (salt).
An equiproportional mixture of dihydroergocornine mesylate,dihydroergocristine mesylate,and ratio of dihydro-a-ergocryptine mesylate to dihydro-b-ergocryptine mesylate is (1.5-2.5:1)
[8067-24-1].
»Ergoloid Mesylates is a mixture of the methanesulfonate salts of the three hydrogenated alkaloids,dihydroergocristine (C35H41N5O5·CH4O3S),dihydroergocornine (C31H41N5O5·CH4O3S),and dihydroergocryptine (C32H43N5O5·CH4O3S),in an approximate weight ratio of 1:1:1.Ergoloid Mesylates contains not less than 97.0percent and not more than 103.0percent of the alkaloid methanesulfonate mixture,calculated on the anhydrous basis,and not less than 30.3percent and not more than 36.3percent of the methanesulfonate salt of each of the individual alkaloids.Dihydroergocryptine mesylate exists as a mixture of alpha-and beta-isomers.The ratio of alpha-to beta-isomers is not less than 1.5:1.0and not more than 2.5:1.0.
Packaging and storage—
Preserve in tight,light-resistant containers.
Identification—
A:
The IRabsorption spectrum of a potassium bromide dispersion of it exhibits maxima only at the same wavelengths as that of a similar,undried preparation of USP Ergoloid Mesylates RS.
B:
In a suitable chromatographic chamber,arranged for thin-layer chromatography,place a volume of a solvent system consisting of a mixture of acetone,n-butyl alcohol,ammonium hydroxide,and water (65:20:10:5)sufficient to develop the chromatogram.Prepare a test solution of Ergoloid Mesylates in a mixture of chloroform and methanol (9:1)containing 40mg per mL.Apply 10µLof this solution and 10µLof a reference solution of methanesulfonic acid containing 0.4mLin 100mLof a mixture of chloroform and methanol (9:1)to a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel.Develop the chromatogram until the solvent front has moved 10cm.Remove the plate from the developing chamber,mark the solvent front,and dry in a current of cold air.Spray the plate with a 1in 1000solution of bromocresol purple in alcohol that previously has been adjusted to the purple color with 6Nammonium hydroxide,then place in a stream of warm air until the spots appear:the RFvalue of the methanesulfonic acid spot obtained from the test solution corresponds to that obtained from the reference solution.
Specific rotation á781Sñ:
between +11.0
and +15.0.
and +15.0.
Test solution:
10mg per mL,in dilute alcohol (1in 2).
pHá791ñ:
between 4.2and 5.2in a solution (1in 200).
Water,Method Iá921ñ:
not more than 5.0%.
Limit of ergotamine—
Prepare three solutions in a mixture of chloroform and methanol (9:1)containing 5mg of Ergoloid Mesylates per mL,5mg of USP Ergoloid Mesylates RSper mL,and 5mg of Ergotamine Tartrate per mL.Apply 5-µLvolumes of the solutions at points about 2cm from the bottom edge of a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture,and allow the spots to dry.Add the solvent system consisting of a mixture of chloroform and methanol (9:1)and a small beaker of ammonium hydroxide to a suitable chamber,seal,and allow to equilibrate for 30minutes.Develop the chromatogram in the equilibrated chamber until the solvent front has moved about 15cm from the points of application.Remove the plate,air-dry,and locate the spots,first by viewing under long-wavelength UVlight,and then by spraying with a reagent prepared by dissolving 800mg of p-(dimethylamino)benzaldehyde in a mixture of 80mLof alcohol and 11mLof sulfuric acid:the chromatogram from Ergoloid Mesylates shows primary spots that correspond in size and color to the spots obtained from the USP Ergoloid Mesylates RSsolution,and shows no spot corresponding to the principal spot in the chromatogram of Ergotamine Tartrate.
Limit of nonhydrogenated alkaloids—
Prepare a solution in alcohol containing 0.4mg of Ergoloid Mesylates per mL,and prepare a 1in 10dilution of the first solution.Determine the absorbances in 1-cm cells of the first solution at 317.5nm and the dilution at 280nm,using alcohol as the blank:the absorbance of the first solution is not more than 0.15times that of the dilution.
Assay—
Mobile phase—
Prepare a degassed solution containing a mixture of water,acetonitrile,and triethylamine (80:20:2.5).Adjust the ratio as necessary.
Standard preparation—
Transfer about 10mg of USP Ergoloid Mesylates RS,accurately weighed,to a 10-mLvolumetric flask.Dissolve in a mixture of acetonitrile and water (1:1),dilute with the same solvent to volume,and mix.Prepare this solution fresh.
Assay preparation—
Using about 10mg of Ergoloid Mesylates,accurately weighed,proceed as directed for Standard preparation.
Chromatographic system
(see Chromatography á621ñ)—The liquid chromatograph is equipped with a 280-nm detector and a 4-mm ×30-cm column that contains packing L1.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the resolution,R,between dihydro-a-ergocryptine mesylate and dihydroergocristine mesylate is not less than 1.35,the resolution,R,between dihydroergocristine and dihydro-b-ergocryptine is not less than 1.0;the column efficiency determined for the dihydro-b-ergocryptine mesylate peak is not less than 950theoretical plates;the tailing factor for dihydro-b-ergocryptine mesylate is not more than 2.5;and the relative standard deviation of the sum of the four peaks for replicate injections is not more than 1.5%.
Procedure—
Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph by means of a suitable microsyringe or sampling valve,record the chromatograms,and measure the responses for the major peaks.The order of elution is dihydroergocornine,dihydro-a-ergocryptine,dihydroergocristine,and dihydro-b-ergocryptine.Calculate the total quantity,in mg,of these alkaloids in the portion of Ergoloid Mesylates taken by the formula:
10C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Ergoloid Mesylates RSin the Standard preparation;and rUand rSare the sums of the responses of the four major peaks obtained from the Assay preparationand the Standard preparation,respectively.
Calculate the percentage of each alkaloid taken by the formula:
100ri(MW)i/S[ri(MW)i],
in which riis the peak response of an individual alkaloid;(MW)iis the molecular weight of that alkaloid;and S[ri(MW)i]is the summation of the products of peak responses and molecular weights calculated for the four alkaloids.
Auxiliary Information—
Staff Liaison:Ravi Ravichandran,Ph.D.,Senior Scientist
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 748
Phone Number:1-301-816-8330