Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Class I antiarrhythmic.
DEFINITION
Flecainide Injection is a sterile solution of Flecainide Acetate in Water for Injections.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of flecainide acetate, C17H20F6N2O3,C2H4O2
95.0 to 105.0% of the stated amount.
CHARACTERISTICS
A clear, colourless or almost colourless solution.
IDENTIFICATION
A. The light absorption, Appendix II B, of the solution obtained in the Assay in the range 230 nm to 350 nm exhibits a maximum at 296 nm.
B. In the test for (Piperidin-2-yl)methanamine, examine the chromatograms under ultraviolet light (254 nm) before spraying. The principal spot in the chromatogram obtained with solution (2) corresponds to that in the chromatogram obtained with solution (3).
TESTS
Acidity
pH, 5.0 to 6.5, Appendix V L.
(Piperidin-2-yl)methanamine
Carry out the method for thin-layer chromatography, Appendix III A, using a silica gel F254 precoated plate (Merck plates are suitable) and a mixture of 2 volumes of methanol, 5 volumes of 18M ammonia, 100 volumes of acetone and 100 volumes of dichloromethane as the mobile phase but allowing the solvent front to ascend 10 cm above the line of application. Apply separately to the plate 1 μL of solution (1) and 5 μL of each of solutions (2) and (3). Solution (1) contains 0.025% w/v of flecainide acetate impurity B EPCRS [(piperidin-2-yl)methanamine] in methanol. For solution (2) dilute the injection, if necessary, with methanol to contain 1% w/v of flecainide acetate. Solution (3) contains 1% w/v of flecainide acetate BPCRS in methanol. After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm) (for Identification test B). Spray the plate with a freshly prepared 0.2% w/v solution of ninhydrin in methanol, heat the plate at 105° for approximately 5 minutes and examine immediately. In the chromatogram obtained with solution (2) any bluish-purple spot corresponding to (piperidin-2-yl)methanamine is not more intense than the spot in the chromatogram obtained with solution (1) (0.5%).
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions. Solution (1) is the injection diluted, if necessary, with a mixture of 29 volumes of acetonitrile and 71 volumes of water to contain 1.0% w/v of flecainide acetate. For solution (2) dilute 1 volume of solution (1) to 100 volumes with a mixture of 29 volumes of acetonitrile and 71 volumes of water and further dilute 1 volume of this solution to 5 volumes with the same solvent mixture. Solution (3) contains 0.01% w/v of each of flecainide acetate BPCRS and flecainide impurity A EPCRS in a mixture of 29 volumes of acetonitrile and 71 volumes of water.
The chromatographic procedure may be carried out using (a) a stainless steel column (15 cm × 4.6 mm) packed with end-capped octylsilyl silica gel for chromatography (5 μm) (Zorbax C8 is suitable), (b) as the mobile phase with a flow rate of 2 mL per minute a mixture of 5 volumes of 1M tetrabutylammonium hydroxide, 10 volumes of glacial acetic acid, 290 volumes of acetonitrile and 710 volumes of water, the mixture adjusted to pH 5.8 using 18M ammonia, and (c) a detection wavelength of 254 nm.
Inject 20 μL of each solution. The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks corresponding to flecainide and flecainide impurity A is at least 3.5.
For solution (1) allow the chromatography to proceed for nine times the retention time of the principal peak. In the chromatogram obtained with solution (1) the area of any secondary peak is not greater than the area of the peak in the chromatogram obtained with solution (2) (0.2%) and the sum of the areas of any such peaks is not greater than two and a half times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%). Disregard any peak with an area less than 0.05 times the area of the peak in the chromatogram obtained with solution (2) (0.01%).
ASSAY
Dilute the injection with a 0.2% v/v solution of lactic acid to produce a solution containing 0.01% w/v of flecainide acetate and measure the absorbance of the resulting solution at the maximum at about 296 nm, Appendix II B, using a 0.2% v/v solution of lactic acid in the reference cell. Calculate the content of C17H20F6N2O3,C2H4O2 in the injection from the absorbance obtained with a solution containing 0.01% w/v of flecainide acetate BPCRS in a 0.2% v/v solution of lactic acid and using the declared content of C17H20F6N2O3,C2H4O2 in flecainide acetate BPCRS.
STORAGE
Flecainide Injection should not be allowed to freeze.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities A, B and D stated under Flecainide Acetate.
