Mexiletine Capsules
Action and use
Class I antiarrhythmic.
Definition
Mexiletine Capsules contain Mexiletine Hydrochloride.
Content of mexiletine hydrochloride, C11H17NO,HCl
92.5 to 107.5% of the stated amount.
Identification
Tests
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) mix, with the aid of ultrasound for 10 minutes, a quantity of the contents of the capsules containing 0.2 g of Mexiletine Hydrochloride with 10 mL of the mobile phase, filter through a 0.4-µm glass microfibre filter (Whatman GF/C is suitable) and use the filtrate. For solution (2) dilute 1 volume of solution (1) to 10 volumes with the mobile phase. For solution (3) dissolve 2 mg of mexiletine impurity C EPCRS and 16 mg of 2,6-dimethylphenol in the mobile phase and add sufficient mobile phase to produce 20 mL. Mix 1 volume of this solution with 2 volumes of solution (2) and add sufficient mobile phase to produce 100 volumes.
The chromatographic procedure may be carried out using (a) a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Hypersil is suitable), (b) as mobile phase with a flow rate of 1 mL per minute a mixture of 35 volumes of solution A described below and 65 volumes of methanol R2 and (c) a detection wavelength of 262 nm. For solution (A) dissolve 11.5 g of anhydrous sodium acetate in 500 mL of water, add 3.2 mL of glacial acetic acid, mix and allow to cool. Adjust the pH to 4.8 with glacial acetic acid and add sufficient water to produce 1000 mL. For solution (1) allow the chromatography to proceed for 5.5 times the retention time of mexiletine.
When the chromatograms are recorded in the prescribed conditions, the retention time of mexiletine is about 4 minutes and retention times relative to mexiletine are about 0.7 for mexiletine impurity C (1,1′-[(3,3′,5,5′-tetramethylbiphenyl-4,4′-diyl)bisoxy]dipropan-2-amine) and about 1.8 for mexiletine impurity A (2,6-dimethylphenol).
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to mexiletine and impurity C is at least 5.0.
In the chromatogram obtained with solution (1) the area of any peak corresponding to impurity A is not greater than 2.5 times the area of the peak due to 2,6-dimethylphenol in the chromatogram obtained with solution (3) (0.1%), the area of any peak corresponding to impurity C is not greater than 20 times the area of the peak due to impurity C in the chromatogram obtained with solution (3) (0.1%), the area of any other secondary peak is not greater than half the area of the peak due to mexiletine in the chromatogram obtained with solution (3) (0.1%) and the sum of the areas of all the peaks is not greater than 2.5 times the area of the peak due to mexiletine in the chromatogram obtained with solution (3) (0.5%). Disregard any peak with an area less than 0.25 times the area of the principal peak in the chromatogram obtained with solution (2) (0.05%).
Assay
Shake a quantity of the mixed contents of 20 capsules containing 50 mg of Mexiletine Hydrochloride with 50 mL of 0.01m hydrochloric acid for 30 minutes. Dilute to 100 mL with 0.01m hydrochloric acid and centrifuge. Measure the absorbance of the supernatant liquid at the maximum at 260 nm, Appendix II B. Calculate the content of C11H17NO,HCl taking 11.6 as the value of A(1%, 1 cm) at the maximum at 260 nm.