A: Infrared Absorption 197M.

B: Prepare a test solution by dissolving a suitable quantity of it in methanol to obtain a concentration of about 10 mg per mL. Similarly prepare a Standard solution, using USP Mexiletine Hydrochloride RS. Separately apply 5-µL portions of the test solution and the Standard solution to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel. Develop the chromatogram in a suitable chromatographic chamber half saturated with solvent vapor, using a solvent system consisting of a mixture of chloroform, methanol, and ammonium hydroxide (425:70:5) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and allow the solvent to evaporate. Spray the plate with a 1 in 500 solution of fast blue BB salt in methanol, and dry the plate at 105 for 15 minutes. Locate the spots on the plate by spraying it with a 1 in 5 solution of potassium hydroxide in methanol: the RF value of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.

C: To 3 mL of a solution (1 in 60) add 1 mL of 6 N ammonium hydroxide, filter, and acidify the filtrate with 2 mL of nitric acid. Then add 1 mL of silver nitrate TS: a curdy, white precipitate is formed, and it is soluble in an excess of 6 N ammonium hydroxide (presence of chloride).

Mobile phase, Standard preparation, and Resolution solution—Prepare as directed in the Assay.

Standard solution— Transfer 10.0 mL of the Standard preparation prepared as directed in the Assay to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix. This solution contains about 0.2 mg of USP Mexiletine Hydrochloride RS per mL.

Test solution— Transfer about 100 mg of Mexiletine Hydrochloride, accurately weighed, to a 5-mL volumetric flask, dilute with Mobile phase to volume, and mix.

Chromatographic system (see Chromatography 621)— Prepare as directed in the Assay, except that the relative standard deviation for replicate injections of the Standard solution is not more than 3.0%.

Procedure— Proceed as directed for Procedure in the Assay. Calculate the percentage of each impurity observed taken by the formula: in which C is the concentration, in mg per mL, of USP Mexiletine Hydrochloride RS in the Standard solution, W is the weight, in mg, of the Mexiletine Hydrochloride taken to prepare the Test solution, rU is the peak response obtained from an individual impurity observed in the chromatogram of the Test solution, and rS is the mexiletine peak response obtained from the Standard solution: not more than 1% of any individual impurity is found, and the total of all observed impurities is not more than 1.5%.

Sodium acetate buffer solution— 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 with hydrochloric acid to a pH of 4.8 ± 0.1, dilute with water to 1000 mL, and mix.

Mobile phase— Prepare a suitable filtered and degassed mixture of methanol and Sodium acetate buffer solution (600:400). Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard preparation— Dissolve an accurately weighed quantity of USP Mexiletine Hydrochloride RS in Mobile phase to obtain a solution having a known concentration of about 2 mg per mL.

Resolution solution— Prepare a solution of 2-phenylethylamine hydrochloride in Standard preparation containing about 1 mg per mL.

Assay preparation— Transfer about 100 mg of Mexiletine Hydrochloride, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.

Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 254-nm detector, a guard column containing packing L1, and a 3.9-mm × 30-cm column that contains 10-µm packing L1. The flow rate is about 1 mL per minute. Chromatograph about 20 µL of the Resolution solution, and record the peak responses as directed under Procedure: the resolution, R, between the 2-phenylethylamine and mexiletine peaks is not less than 3.0. Chromatograph the Standard preparation, and record the peak responses as directed under Procedure: the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— [note—Use peak areas where peak responses are indicated.] Separately inject equal volumes (about 20 µL) of the Assay preparation and the Standard preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The relative retention times are about 0.7 for 2-phenylethylamine and 1.0 for mexiletine. Calculate the quantity, in mg, of C11H17NO·HCl in the portion of Mexiletine Hydrochloride taken by the formula: in which C is the concentration, in mg per mL, of USP Mexiletine Hydrochloride RS in the Standard preparation, and rU and rS are the mexiletine peak responses obtained from the Assay preparation and the Standard preparation, respectively.