Bromocriptine Mesylate Tablets
»Bromocriptine Mesylate Tablets 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.
Labeling— The labeling indicates the Dissolution Testwith which the product complies.
Identification— Examine the chromatograms obtained in the test for Related compounds:the principal spot obtained from the test solution is similar in RFvalue,and color to that obtained from the Standard solution.
Dissolution á711ñ—
Test 1: If the product complies with this test,the labeling indicates that it meets USPDissolution Test 1.
Medium: 0.1Nhydrochloric acid;500mL.
Apparatus 1: 120rpm.
Time: 60minutes.
Procedure— Determine the amount in solution in portions of the solution under test that previously have been passed through a glass-fiber filter from fluorometric measurements at an excitation wavelength of 315nm and an emission wavelength of 445nm,using Dissolution Mediumas the blank,in comparison with a Standard solution having a known concentration of USP Bromocriptine Mesylate RSin the same Medium.Avolume of alcohol not to exceed 5%of the total volume of the Standard solution may be used to bring the standard into solution prior to dilution with 0.1Nhydrochloric acid.
Tolerances— Not less than 80%(Q)of the labeled amount of bromocriptine (C32H40BrN5O5)is dissolved in 60minutes.
Test 2: If the product complies with this test,the labeling indicates that it meets USPDissolution Test 2.
Medium: 0.1Nhydrochloric acid;500mL.
Apparatus 2: 50rpm.
Time: 30minutes.
Standard preparation— Dissolve an accurately weighed quantity of USP Bromocriptine Mesylate RSin methanol,and quantitatively dilute with Dissolution Mediumto obtain a solution having a known concentration similar to the expected concentration of the test solution.
Mobile phase— Prepare a filtered and degassed mixture of acetonitrile and 0.01Mammonium carbonate (65:35).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Chromatography system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 300-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1.5mLper minute.Chromatograph replicate injections of the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation is not more than 2.0%.
Procedure— Separately inject equal volumes (about 100µL)of the Standard preparationand the solution under test into the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity of C32H40BrN5O5dissolved by comparison of the peak responses obtained from the Standard preparationand the solution under test.
Tolerances— Not less than 80%(Q)of the labeled amount of bromocriptine (C32H40BrN5O5)is dissolved in 30minutes.
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 1Tablet into a 25-mLvolumetric flask.Add about 15mLof Solvent solution,and shake by mechanical means for 30minutes.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 Tablet 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 Tablet;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 Tablet,based upon the labeled quantity per Tablet and the extent of dilution;and AUand ASare the absorbances of the solution from the Tablet 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 applying the test solution last.]Transfer a quantity of finely powdered Tablets,equivalent to 20mg of bromocriptine,to a conical flask.Add 10.0mLof methanol,and mix for 20minutes.Centrifuge the suspension at 4000rpm for 10minutes.The clear supernatant is the test solution.Similarly prepare a Standard solution of USP Bromocriptine Mesylate RSin methanol containing 1mg of bromocriptine per mLand 3Standard dilutions having final concentrations equivalent to 0.10,0.30,and 0.50mg of bromocriptine per mL(equivalent to 1.0,3.0,and 5.0%,respectively).Separately apply,as 1.5-cm bands,10-µLportions of the Standard solution and of the 3Standard dilutions,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.Dry the plate for 5minutes in a current of cold air.Develop in a tank lined with filter paper,previously equilibrated for 20minutes,using a solvent system consisting of a mixture of methylene chloride,dioxane,alcohol,and ammonium hydroxide (180:15:5:0.1)until the solvent front has moved a distance of 10cm on the plate.Dry the plate under vacuum at room temperature for 15minutes.Spray evenly with a 0.2%solution of o-phthalaldehyde in sulfuric acid,and view the plate under long-wavelength UVlight.Any spot,other than the principal spot,obtained from the test solution is not greater in size and intensity than the spot obtained from the 3.0%Standard solution;and any remaining spots are not greater in size and intensity than the spot obtained from the 1.0%Standard solution.The sum of the related compounds is not greater than 5.0%.
Assay—
Mobile phase— Mix 650mLof acetonitrile with 350mLof 0.01Mammonium carbonate.
Standard preparation— Transfer about 11mg of USP Bromocriptine Mesylate RS,accurately weighed,to a 50-mLvolumetric flask,dissolve in and dilute with methanol to volume,and mix.
Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 10mg of bromocriptine,to an appropriate container,add 40mLof methanol,and stir for 20minutes,protected from light.Quantitatively filter through a fine glass filtering funnel into a 50-mLvolumetric flask.Rinse the filter with methanol,adding the rinsing to the filtrate,dilute with methanol to volume,and mix.
Procedure— Separately inject equal volumes (about 50µL)of the Standard preparationand the Assay preparationinto a high-performance liquid chromatograph equipped with a 250-×4-mm stainless steel column containing packing L1,an UVdetector capable of monitoring absorption at 300nm,and suitable recorder and integrator.The column is maintained at ambient temperature,and the flow rate is adjusted to approximately 2mLper minute.The coefficient of variation for 3replicate injections of the Standard preparationis not more than 3.0%.Calculate the quantity,in mg,of bromocriptine (C32H40BrN5O5)in the portion of Tablets taken by the formula:
(654.59/750.70)50C(AU/AS),
in which 654.59and 750.70are the molecular weights of bromocriptine and bromocriptine mesylate,respectively;Cis the concentration,in mg per mL,of USP Bromocriptine Mesylate RSin the Standard preparation;and AUand ASare the peak areas 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 284
Phone Number:1-301-816-8139