Bromocriptine Mesylate Capsules
» Bromocriptine Mesylate Capsules contain bromocriptine mesylate (C32H40BrN5O5·CH4SO3) equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amount of bromocriptine (C32H40BrN5O5).
Packaging and storage Preserve in tight, light-resistant containers.
USP Reference standards 11
Identification Examine the chromatograms obtained in the test for Related compounds: the principal spot obtained from the test solution corresponds, in RF value and color, to that obtained from the Standard solution.
Medium: 0.1 N hydrochloric acid; 500 mL.
Apparatus 2: 50 rpm.
Time: 60 minutes.
Procedure Determine the amount of bromocriptine mesylate (C32H40BrN5O5·CH4SO3) dissolved using the Procedure for Dissolution Test 1 under Bromocriptine Mesylate Tablets, making any necessary volumetric adjustments.
Tolerances Not less than 75% (Q) of the labeled amount of bromocriptine mesylate (C32H40BrN5O5·CH4SO3) is dissolved in 60 minutes.
Uniformity of dosage units 905: meet the requirements.
procedure for content uniformity [CautionProtect all solutions from light. ]
Solvent solution Dissolve 1.0 g of tartaric acid in 500 mL of water, add 500 mL of methanol, and mix.
Standard solution Using an accurately weighed quantity of USP Bromocriptine Mesylate RS, prepare a solution in the Solvent solution having a known concentration of about 0.04 mg per mL.
Test solution Transfer the contents of 1 Capsule into a 25-mL volumetric flask. Add about 15 mL of Solvent solution, and shake by mechanical means for 20 minutes. Dilute with Solvent solution to volume, and mix. Filter and dilute 10.0 mL of the clear filtrate with Solvent solution to 50.0 mL.
Procedure Concomitantly determine the absorbances of the Test solution and the Standard solution in 1-cm cells at the wavelength of maximum absorbance at about 306 nm, with a suitable spectrophotometer, using Solvent solution as 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 654.59 and 750.70 are the molecular weights of bromocriptine and bromocriptine mesylate, respectively; T is the labeled quantity, in mg, of bromocriptine in the Capsule; C is the concentration, in µg per mL, of USP Bromocriptine Mesylate RS in the Standard solution; D is 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 AU and AS are the absorbances of the solution from the Capsule and the Standard solution, respectively.
Related compounds [noteConduct 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 20 mg of bromocriptine, to a conical flask. Add 10 mL of methanol, and stir by mechanical means for 20 minutes. Centrifuge the suspension for 10 minutes at about 3500 rpm. The clear supernatant is the test solution. Prepare a Standard solution of USP Bromocriptine Mesylate RS in methanol containing the equivalent of 2 mg 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 0.06 mg, 0.04 mg, 0.02 mg, and 0.01 mg of bromocriptine per mL (equivalent to 3.0%, 2.0%, 1.0%, and 0.5%, respectively). Separately apply, as 1.5-cm bands, 50-µL portions of the Standard solution and of each of the four diluted Standard solutions and 50 µL of the test solution, to a suitable thin-layer chromatographic plate (see Chromatography 621) 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 30 minutes, 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 15 cm on the plate. Dry the plate briefly in a current of cold air. Spray evenly with a 2 in 1000 solution of o-phthalaldehyde in sulfuric acid, and view the plate under long-wavelength UV light. 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 [noteConduct this procedure without exposure to daylight and with minimum exposure to artificial light. ]
Mobile phase Dissolve 100 mg of ammonium carbonate in 800 mL of water. Prepare a filtered and degassed mixture of acetonitrile and the ammonium carbonate solution (3:2). Make adjustments if necessary (see System Suitability under Chromatography 621).
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 1.0 mg per mL of the bromocriptine.
Assay preparation Remove, as completely as possible, the contents of not fewer than 10 Capsules. 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 50 mg of bromocriptine, to a 50-mL volumetric flask. Add about 30 mL of dehydrated alcohol, and shake for 15 minutes. Dilute with dehydrated alcohol to volume, mix, and filter. [noteUse this preparation without delay. ]
Chromatographic system (see Chromatography 621)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 2 mL per 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 1000 theoretical 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 20 µL) of the Standard preparation and the Assay preparation into 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 C is the concentration, in mg per mL, of USP Bromocriptine Mesylate RS in the Standard preparation, expressed as bromocriptine; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 2388Pharmacopeial Forum: Volume No. 32(1) Page 58