Bromocriptine Mesylate Capsules
»Bromocriptine Mesylate Capsules contain bromocriptine mesylate (C32H40BrN5O5·CH4SO3)equivalent to not less than 90.0percent and not more than 110.0percent of the labeled amount of bromocriptine (C32H40BrN5O5).
Packaging and storage— Preserve in tight,light-resistant containers.
Identification— Examine the chromatograms obtained in the test for Related compounds:the principal spot obtained from the test solution corresponds,in RFvalue and color,to that obtained from the Standard solution.
Dissolution á711ñ—
Medium: 0.1Nhydrochloric acid;500mL.
Apparatus 2: 50rpm.
Time: 60minutes.
Procedure— Determine the amount of Bromocriptine Mesylate dissolved using the Proceduregiven under Dissolutionfor Bromocriptine Mesylate Tablets,making any necessary volumetric adjustments.
Tolerances— Not less than 75%(Q)of the labeled amount of bromocriptine is dissolved in 60minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Procedure for content uniformity— [Caution—Protect all solutions from light ]
Solvent solution— Dissolve 1.0g of tartaric acid in 500mLof water,add 500mLof methanol,and mix.
Standard solution— Using an accurately weighed quantity of USP Bromocriptine Mesylate RS,prepare a solution in the Solvent solutionhaving a known concentration of about 0.04mg per mL.
Test solution— Transfer the contents of 1Capsule into a 25-mLvolumetric flask.Add about 15mLof Solvent solution,and shake by mechanical means for 20minutes.Dilute with Solvent solutionto volume,and mix.Filter and dilute 10.0mLof the clear filtrate with Solvent solutionto 50.0mL.
Procedure— Concomitantly determine the absorbances of the Test solutionand the Standard solutionin 1-cm cells at the wavelength of maximum absorbance at about 306nm,with a suitable spectrophotometer,using Solvent solutionas the blank.Calculate the quantity,in mg,of bromocriptine (C32H40BrN5O5)in the Capsule taken by the formula:
(654.59/750.70)(TC/D)(AU/AS),
in which 654.59and 750.70are the molecular weights of bromocriptine and bromocriptine mesylate,respectively;Tis the labeled quantity,in mg,of bromocriptine in the Capsule;Cis the concentration,in µg per mL,of USP Bromocriptine Mesylate RSin the Standard solution;Dis the concentration,in µg per mL,of bromocriptine in the solution from the Capsule,based upon the labeled quantity per Capsule and the extent of dilution;and AUand ASare the absorbances of the solution from the Capsule and the Standard solution,respectively.
Related compounds— [NOTE—Conduct this test without exposure to daylight and with minimum exposure to artificial light.Perform the test rapidly,preparing and spotting the test solution last.]Transfer a quantity of capsule contents,equivalent to 20mg of bromocriptine,to a conical flask.Add 10mLof methanol,and stir by mechanical means for 20minutes.Centrifuge the suspension for 10minutes at about 3500rpm.The clear supernatant is the test solution.Prepare a Standard solution of USP Bromocriptine Mesylate RSin methanol containing the equivalent of 2mg of bromocriptine per mL.Dilute quantitatively,and stepwise if necessary,the Standard solution with methanol to obtain four diluted Standard solutions having final concentrations of 0.06mg,0.04mg,0.02mg,and 0.01mg of bromocriptine per mL(equivalent to 3.0%,2.0%,1.0%,and 0.5%,respectively).Separately apply,as 1.5-cm bands,50-µLportions of the Standard solution and of each of the four diluted Standard solutions and 50µLof the test solution,to a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Develop under the exclusion of light in a tank lined with filter paper,previously equilibrated for 30minutes,using a solvent system consisting of a mixture of methylene chloride,dioxane,alcohol,and ammonium hydroxide (180:15:5:1)until the solvent front has moved a distance of 15cm on the plate.Dry the plate briefly in a current of cold air.Spray evenly with a 2in 1000solution of o-phthalaldehyde in sulfuric acid,and view the plate under long-wavelength UVlight.Any major secondary spot,other than the principal spot,obtained from the test solution is not greater in size and intensity than the spot obtained from the diluted Standard solution corresponding to 3.0%,and any remaining spots are not greater in size and intensity than the spot obtained from the diluted Standard solution corresponding to 1.0%.The sum of the related substances is not greater than 5.0%.
Assay— [NOTE—Conduct this procedure without exposure to daylight and with minimum exposure to artificial light.]
Mobile phase— Dissolve 100mg of ammonium carbonate in 800mLof water.Prepare a filtered and degassed mixture of acetonitrile and the ammonium carbonate solution (3:2).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Using an accurately weighed quantity of USP Bromocriptine Mesylate RS,prepare a solution in dehydrated alcohol,using sonication if necessary,having a known concentration of about 1.0mg per mLof the bromocriptine.
Assay preparation— Remove,as completely as possible,the contents of not fewer than 10Capsules.Weigh the contents,and determine the average weight per Capsule.Mix the combined contents,and transfer an accurately weighed quantity of the powder,equivalent to about 50mg of bromocriptine,to a 50-mLvolumetric flask.Add about 30mLof dehydrated alcohol,and shake for 15minutes.Dilute with dehydrated alcohol to volume,mix,and filter.[NOTE—Use this preparation without delay.]
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 300-nm detector and a 4-mm ×25-cm column that contains packing L7.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency determined from the analyte peak is not less than 1000theoretical 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.Calculate the quantity,in mg,of bromocriptine (C32H40BrN5O5)in the Capsules taken by the formula:
50C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Bromocriptine Mesylate RSin the Standard preparation,expressed as bromocriptine;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 283
Phone Number:1-301-816-8139