Co-beneldopa Capsules
Action and use
Dopa decarboxylase inhibitor + dopamine precursor; treatment of Parkinson’s disease.
Definition
Co-beneldopa Capsules contain Benserazide Hydrochloride and Levodopa in the proportions, by weight, 1 part benserazide to 4 parts levodopa.
Content of benserazide, C10H15N3O5
95.0 to 105.0% of the stated amount.
Content of levodopa, C9H11NO4
95.0 to 105.0% of the stated amount.
Identification
10 volumes of a 10% v/v solution of hydrochloric acid, 20 volumes of water and 70 volumes of propan-2-ol.
The chromatogram obtained with solution (1) shows two clearly separated spots, the spot with the higher Rf value corresponding to the spot in the chromatogram obtained with solution (2) and the spot with the lower Rf value corresponding to the spot in the chromatogram obtained with solution (3).
Tests
Dissolution
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
The chromatographic conditions described under Assay may be used. Disregard the peak due to benserazide.
Calculate the total content of levodopa, C9H11NO4, in the medium using the declared content of C9H11NO4 in levodopa BPCRS.
Related substances
Dissolve 4.76 g of potassium dihydrogen orthophosphate in 800 mL of water, add 200 mL of acetonitrile and 1.22 g of sodium decanesulfonate and adjust the pH to 3.5 with orthophosphoric acid.
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to benserazide (retention time about 7 minutes) are: levodopa, about 0.3; benserazide impurity A, about 0.7; benserazide impurity B, about 3.2.
The test is not valid unless, in the chromatogram obtained with solution (2), the resolution between the peaks due to benserazide and impurity A is at least 2.0.
In the chromatogram obtained with solution (1):
the area of any peak corresponding to benserazide impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the area of any peak corresponding to benserazide impurity B is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the area of any other secondary peak is not greater than 0.4 times the area of the peak due to benserazide in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any secondary peaks is not greater than three times the area of the peak due to benserazide in the chromatogram obtained with solution (2) (1.5%).
Disregard any peak with an area less than 0.2 times the area of the peak due to benserazide in the chromatogram obtained with solution (2) (0.1%).
10 volumes of a 10% v/v solution of hydrochloric acid, 20 volumes of water and 70 volumes of propan-2-ol.
The test is not valid unless the chromatogram obtained with solution (3) shows a distinct band, at a higher Rf value than the principal band, which is more intense than the band in the chromatogram obtained with solution (2).
Any secondary band in the chromatogram obtained with solution (1) is not more intense than the band in the chromatogram obtained with solution (2) (0.5%).
Assay
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
Dissolve 4.76 g of potassium dihydrogen orthophosphate in 800 mL of water, adding 200 mL of acetonitrile and 1.22 g of sodium decanesulfonate and adjusting the pH to 3.5 with orthophosphoric acid.
The chromatogram obtained with solution (2) shows two principal peaks; the retention time of the peak due to benserazide is about three times that of the peak due to levodopa.
Calculate the content of C10H15N3O5 and of C9H11NO4 in each capsule using the declared contents of C10H15N3O5 in benserazide hydrochloride BPCRS and of C9H11NO4 in levodopa BPCRS.
Storage
Co-beneldopa Capsules should protected from moisture.
Labelling
The quantity of Benserazide Hydrochloride is stated in terms of the equivalent amount of benserazide.
Impurities
The impurities limited by the requirements of this monograph include impurities A and B listed under Benserazide Hydrochloride.