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1714 Amantadine/ Official Monographs USP 37

Column temperature: See Table 1. IDENTIFICATION INFRAREDABSORPTION197S

Cell: 1 mmTable 1Sample solution: Place the contents of Capsules, equiv-

Hold Time at alent to 200 mg of amantadine hydrochloride, in a ves-Initial Temperature Final Final sel, dissolve in 0.1 N hydrochloric acid, and filter. Trans-

Temperature Ramp Temperature Temperature fer the filtrate to a separator, add 1 mL of 5 N sodium() (/min) () (min) hydroxide, and extract with 5 mL of methylene chlo-

70 0 70 5 ride. Filter the extract through anhydrous sodium sul-fate, and rinse the anhydrous sodium sulfate with 2 mL70 10 250 At least 17of methylene chloride.

Carrier gas: HeliumASSAYFlow rate: 4 mL/min PROCEDUREInjection size: 2 L

Internal standard solution: 0.4 mg/mL of naphthaleneInjector temperature: 220in hexaneInjection type:

Standard stock solution: 2 mg/mL of USP AmantadineSplit flow: 200 mL/minHydrochloride RS in waterSplit flow ratio: 50:1

Standard solution: Pipet 25.0 mL of Standard stock so-System suitabilitylutioninto a 250-mL separator, and add 25 mL of 2.0 NSample: Standard solutionsodium hydroxide and 50.0 mL of Internal standard so-[NOTEThe relative retention times for adamantane andlution. Shake for 60 min, and collect the hexane layeramantadine are about 0.7 and 1.0, respectively.](Standard solution).Suitability requirements

Sample solution: Transfer NLT 20 Capsules to aResolution: NLT 20 between adamantane and200-mL volumetric flask. Add 40 mL of 0.1 N hydro-amantadine

chloric acid, and heat gently to achieve complete disso-Relative standard deviation: NMT 5.0% determined lution. Cool, and dilute with water to volume. Pipetfrom the peak response ratios of amantadine to5.0 mL of the solution into a 250-mL separator, andadamantaneadd 40 mL of 1.0 N sodium hydroxide and 50.0 mL ofAnalysisInternal standard solution. Shake for 60 min, and collectSamples: Standard solutionand Sample solutionthe hexane layer (Sample solution).Calculate the percentage of each impurity in the por-

Chromatographic systemtion of amantadine hydrochloride (C10H17N HCl)(See Chromatography 621, System Suitability.)taken:Mode: GCDetector: Flame ionizationResult = (RU/RS) (CS/CU) 100Column: 2-mm 1.22-m; glass column packed with

RU = peak response ratio of each impurity to 10% phase G1 on 100- to 120-mesh support S1Aadamantane from the Sample solution Temperature

RS = peak response ratio of amantadine to Column: 115adamantane from the Standard solution Injector: 250

CS = concentration of USP Amantadine Detector block: 250Hydrochloride RS in the Standard solution Injection size: 1 L

(mg/mL) System suitabilityCU = concentration of the Sample solution(mg/mL) Sample: Standard solutionAcceptance criteria Suitability requirementsIndividual impurities: NMT 0.3% Resolution: NLT 2 between napthalene andTotal impurities: NMT 1.0% amantadine

Tailing factor: NMT 2.0 for the analyte peakSPECIFIC TESTS Relative standard deviation: NMT 2.0% PH 791 Analysis

Sample: 0.2 g/mL in water Samples: Standard solutionand Sample solutionAcceptance criteria: 3.05.5 Calculate the percentage of C10H17N HCl in the por-

CLARITYANDCOLOROFSOLUTION tion taken:Sample: Dissolve 2 g in 10 mL of water.Acceptance criteria: Solution is clear and nearly Result = (RU/RS) (CS/CU) 100colorless.

RU = peak response ratios from the Sample solutionADDITIONAL REQUIREMENTS RS = peak response ratios from the Standard PACKAGINGANDSTORAGE: Preserve in well-closed solution

containers.CS = concentration of USP Amantadine USP REFERENCESTANDARDS11 Hydrochloride RS in the Standard solution

USP Amantadine Hydrochloride RS (mg/mL)CU = nominal concentration of the Sample solution

(mg/mL)Acceptance criteria: 95.0%105.0%

.

PERFORMANCE TESTSAmantadine Hydrochloride Capsules DISSOLUTION711

Test 1: Procedure for a Pooled SampleDEFINITIONMedium: Water; 900 mLAmantadine Hydrochloride Capsules contain NLT 95.0% andApparatus 1: 100 rpmNMT 105.0% of the labeled amount of amantadine hy-Time: 45 mindrochloride (C10H17N HCl).Internal standard solution: 0.054 mg/mL of naphtha-lene in hexane

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7/25/2019 Amantadine HCL Capsules

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USP 37 Official Monographs /Amantadine 1715

Standard stock solution: 0.1 mg/mL of USP RU = ratio of the peak areas from the SampleAmantadine Hydrochloride RS in water solutionStandard solution: Pipet 15.0 mL of Standard stock so- RS = average ratio of the peak areas from thelutioninto a 50-mL screw-capped test tube, add Standard solution5.0 mL of 5 N sodium hydroxide and 10.0 mL of Inter- CS = concentration of amantadine hydrochloride innal standard solution, and shake for 60 min. Collect the Standard stock solution(mg/mL)the hexane layer. L = label claim (mg/capsule)

Sample solution: Filter 15.0 mL of the solution under V = volume of Medium, 900 mL

test, and place into a 50-mL screw-capped test tube. Tolerances: NLT 75% (Q) of the labeled amount ofPipet 5.0 mL of 5 N sodium hydroxide and 10.0 mL of amantadine hydrochloride is dissolved.the Internal standard solutioninto the test tube, and UNIFORMITYOFDOSAGEUNITS905: Meet theshake for 60 min. Collect the hexane layer (Sample requirementssolution).

ADDITIONAL REQUIREMENTSChromatographic system: Proceed as directed in the PACKAGINGANDSTORAGE: Preserve in tight containers.Assay. LABELING: When more than one Dissolution test is given,Injection size: 2.5 L

the labeling states the Dissolution test used only if Test 1Analysisis not used.Samples: Standard solutionand Sample solution

USP REFERENCESTANDARDS11Tolerances: NLT 75% (Q) of the labeled amount ofUSP Amantadine Hydrochloride RSC10H17N HCl is dissolved.

Test 2: If the product complies with this test, the label-ing indicates that it meets USP Dissolution Test 2.Medium: Water; 900 mLApparatus 2: 75 rpm, with sinkers. [NOTEA suitable

.

sinker is available as catalog number CAPWHT-2S from

Amantadine Hydrochloride Oralwww.qla-llc.com or www.tabletdissolution.com or Solutionwww.labhut.com.]Time: 45 min

Amantadine Hydrochloride Oral Solution con-Internal standard solution: 0.06 mg/mL of naphtha-lene in hexanes tains not less than 95.0 percent and not more

Standard stock solution: 0.12 mg/mL of USP than 105.0 percent of the labeled amount ofAmantadine Hydrochloride RS in Medium amantadine hydrochloride (C10H17N HCl).Standard solution: Transfer 60.0 mL of the Standardstock solutionto a 200-mL volumetric flask. Add 20 mL Packaging and storagePreserve in tight containers.of 5 N sodium hydroxide and 40.0 mL of Internal stan-

USP Reference standards 11dard solution. Shake the flask for approximately 10USP Amantadine Hydrochloride RSmin, and allow the layers to separate. Use the topIdentification, Infrared Absorption 197Slayer for injection. The final concentration is about

0.18 mg/mL. Cell: 1 mm.Sample solution: Transfer 3.0 mL of the solution SolutionPlace a volume of Oral Solution, equivalent tounder test to a centrifuge tube. Add 1.0 mL of 5 N about 200 mg of amantadine hydrochloride, in a vessel, dis-sodium hydroxide and 2.0 mL of Internal standard solu- solve in 0.1 N hydrochloric acid, and filter. Transfer the fil-tion. Shake the tube for approximately 10 min, and trate to a separator, add 10 mL of 0.5 N sodium hydroxide,allow the layers to separate. Use the top layer for and extract with 5 mL of methylene chloride. Filter the ex-injection. tract through anhydrous sodium sulfate, and rinse the anhy-

Chromatographic system drous sodium sulfate with 2 mL of methylene chloride.(See Chromatography 621, System Suitability.)

AssayMode: GCInternal standard solution,Standard preparation, andChro-Detector: Flame ionization

matographic systemProceed as directed in the AssayunderColumn: 0.32-mm 30-m, 0.25-m film, phase G1Amantadine Hydrochloride Capsules.Temperature

Oven: 100for 3 min, to 200at 10/min, held at Assay preparationPipet 5.0 mL of the Oral Solution into200for 2 min a 250-mL conical flask, and add 45 mL of 1.0 N sodium

Injector: 250 hydroxide and 50.0 mL of Internal standard solution. ShakeDetector: 300 for 60 minutes, and collect the hexane layer (Assay prepara-

Carrier gas: Helium, 1.4 mL/min tion).Flow rate: 20 mL/min ProcedureProceed as directed in the AssayunderInjection size: 2 L Amantadine Hydrochloride Capsules. Calculate the quantity, in

System suitability mg, of amantadine hydrochloride (C10H17N HCl) in the por-Sample: Standard solution tion of Oral Solution taken by the formula:Suitability requirementsResolution: NLT 2 between naphthalene and 50C(RU / RS)amantadine hydrochloride

Tailing factor: NMT 2.0 for amantadine in which Cis the concentration, in mg per mL, of USPhydrochloride Amantadine Hydrochloride RS in the Standard preparation;

Relative standard deviation: NMT 2.0% and RUand RSare the peak response ratios obtained fromAnalysis the Assay preparationand the Standard preparation,respec-Samples: Standard solutionand Sample solution tively.Calculate the percentage of amantadine hydrochlo-ride released:

Result = (RU/RS) (CS/L) V 100

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