Colistin Tablets
Action and use
Antibacterial.
Definition
Colistin Tablets contain Colistin Sulfate.
Identification
To a quantity of the powdered tablets containing 200,000 IU add 10 mL of water, shake and filter. Use the filtrate for the following tests.
25 volumes of water and 75 volumes of phenol.
The bands in the chromatogram obtained with solution (1) correspond to those in the chromatograms obtained with solutions (2) and (3) and do not correspond to those in the chromatograms obtained with solutions (4) and (5). The chromatogram obtained with solution (1) also shows a band with a very low Rf value (2,4-diaminobutanoic acid).
Composition
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
22 volumes of acetonitrile and 78 volumes of a solution prepared by dissolving 4.46 g of anhydrous sodium sulfate in 900 mL of water, adjusting the pH to 2.4 with dilute orthophosphoric acid and adding sufficient water to produce 1000 mL.
Use the chromatogram supplied with colistin sulfate EPCRS to identify the peaks due to polymyxins E1, E2, E3, E1-I and E1-7MOA.
When the chromatograms are recorded under the prescribed conditions the retention time of polymyxin E1 is about 16 minutes. The retention times relative to polymyxin E1 are: polymyxin E2, about 0.45; polymyxin E3, about 0.5; polymyxin E1-I, about 0.8; polymyxin E1-7MOA, about 1.1.
The test is not valid unless, in the chromatogram obtained with solution (2):
the resolution factor between the peaks due to polymyxins E2 and E1 is at least 8.0;
the resolution factor between the peaks due to polymyxins E2 and E1-I is at least 6.0;
the resolution factor between the peaks due to polymyxins E1-I and E1 is at least 2.5;
the resolution factor between the peaks due to polymyxins E1 and E1-7MOA is at least 1.5.
Calculate the content of polymyxin E3, polymyxin E1-I and polymyxin E1-7MOA and the sum of the contents of polymyxins E1, E2, E3, E1-I and E1-7MOA using the declared contents of polymyxins E1, E2, E3, E1-I and E1-7MOA in colistin sulfate EPCRS.
The content of polymyxin E1-I is not more than 10.0%;
the content of polymyxin E1-7MOA is not more than 10.0%;
the content of polymyxin E3 is not more than 10.0%;
the sum of the contents of polymyxin E1, polymyxin E2, polymyxin E3, polymyxin E1-I and polymyxin E1-7MOA is not less than 77.0%.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
The chromatographic conditions described under Composition may be used.
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than 4.0% by normalisation;
the sum of the areas of all secondary peaks is not greater than 23.0% by normalisation.
Disregard any peak with an area less than the area of the peak due to polymyxin E1 in the chromatogram obtained with solution (2) (1%) and any peaks due to polymyxins E1, E2, E3, E1-I and E1-7MOA.
Assay
Weigh and powder 20 tablets. Dissolve a suitable quantity of the powder in phosphate buffer pH 6.0 and carry out the microbiological assay of antibiotics, Appendix XIV A. The precision of the assay is such that the fiducial limits of error are not less than 95% and not more than 105% of the estimated potency. The upper fiducial limit of error is not less than 97.0% and the lower fiducial limit of error is not more than 110.0% of the stated number of IU.
Storage
Colistin Tablets should be protected from light.
Labelling
The strength is stated as the number of IU (units) in each tablet.