Cell: 1 mm.

Solution— Place the contents of Capsules, equivalent to about 200 mg of amantadine hydrochloride, in a vessel, dissolve in 0.1 N hydrochloric acid, and filter. Transfer the filtrate to a separator, add 1 mL of 5 N sodium hydroxide, and extract with 5 mL of methylene chloride. Filter the extract through anhydrous sodium sulfate, and rinse the anhydrous sodium sulfate with 2 mL of methylene chloride.

Medium: water; 900 mL.

Apparatus 1: 100 rpm.

Time: 45 minutes.

Internal standard solution— Dissolve an accurately weighed quantity of naphthalene in hexane to obtain a solution having a known concentration of about 0.054 mg per mL.

Standard solution— Dissolve an accurately weighed quantity of USP Amantadine Hydrochloride RS in water to obtain a solution having a known concentration of about 0.1 mg per mL. Pipet 15.0 mL of this solution into a 50-mL screw-capped test tube, add 5.0 mL of 5 N sodium hydroxide and 10.0 mL of Internal standard solution, and shake for 60 minutes. Collect the hexane layer.

Test solution— Filter 15.0 mL of the solution under test and place into a 50-mL screw-capped test tube. Pipet 5.0 mL of 5 N sodium hydroxide and 10.0 mL of the Internal standard solution into the test tube, and shake for 60 minutes. Collect the hexane layer (Test solution).

Chromatographic system— Proceed as directed under the Assay.

Procedure— Separately inject equal volumes (about 2.5 µL) of the Standard solution and the Test solution. Record the chromatograms, and measure the responses for the major peaks. Calculate the amount of C10H17N·HCl dissolved.

Tolerances— Not less than 75% (Q) of the labeled amount of C10H17N·HCl is dissolved in 45 minutes.

(Official January 1, 2007)

Internal standard solution— Dissolve a quantity of naphthalene in hexane to obtain a solution having a concentration of about 0.4 mg per mL.

Standard preparation— Transfer about 200 mg, accurately weighed, of USP Amantadine Hydrochloride RS to a 100-mL volumetric flask, dissolve in and dilute with water to volume, and mix. Pipet 25.0 mL of this solution into a 250-mL separator, add 25 mL of 2.0 N sodium hydroxide and 50.0 mL of Internal standard solution. Shake for 60 minutes, and collect the hexane layer (Standard preparation).

Assay preparation— Transfer not fewer than 20 Capsules to a 200-mL volumetric flask. Add 40 mL of 0.1 N hydrochloric acid, and heat gently to achieve complete dissolution. Cool, and dilute with water to volume. Pipet 5.0 mL of the solution into a 250-mL separator, and add 40 mL of 1.0 N sodium hydroxide and 50.0 mL of Internal standard solution. Shake for 60 minutes, and collect the hexane layer (Assay preparation).

Chromatographic system (see Chromatography 621)—The gas chromatograph is equipped with a flame-ionization detector and a 2-mm × 1.22-m glass column packed with 10% phase G1 on 100- to 120-mesh support S1A. The column is maintained at about 115, and the injection port and detector block are maintained at about 250. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the resolution, R, between napthalene and amantadine is not less than 2, the tailing factor for the analyte peak is not more than 2.0, and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 1 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for all of the peaks. Calculate the quantity, in mg, of amantadine hydrochloride (C10H17N·HCl) in the portion of Capsules taken by the formula: in which C is the concentration, in mg per mL, of USP Amantadine Hydrochloride RS in the Standard preparation; and RU and RS are the peak response ratios obtained from the Assay preparation and the Standard preparation, respectively.