»Levmetamfetamine contains not less than 98.0percent and not more than 100.5percent of C10H15N.
Packaging and storage Preserve in tight,light-resistant containers.
A: Infrared Absorption á197Fñ.
B: The retention time of the major peak in the chromatogram of the Test solutioncorresponds to that in the chromatogram of the System suitability solution,as obtained in the test for Limit of methamphetamine.
Specific rotation á781Sñ: between -18.5and -21.5.
Test solution: 16mg per mL,in 1.2Nhydrochloric acid.
Limit of methamphetamine
Mobile phase Prepare a filtered and degassed mixture of hexane,isopropyl alcohol,and acetonitrile (98:1.5:0.5).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Resolution solution Mix suitable quantities of a solution of USP Methamphetamine Hydrochloride RSin chloroform and USP Levmetamfetamine RSin chloroform to obtain a solution containing about 0.025mg per mLand 2.5mg per mLof methamphetamine hydrochloride and levmetamfetamine,respectively.Transfer 2.0mLof this solution to a suitable container,add 10mg of 2-naphthyl chloroformate and 2.0mLof chloroform,mix with a vortex mixer,and allow to stand for 5minutes.To this solution,add 2mLof 1Nsodium hydroxide,mix with a vortex mixer,allow to stand for 5minutes,and discard the aqueous layer.Wash the organic layer twice with 2mLof 1Nsodium hydroxide,discarding the aqueous layer.To the organic layer add 2mLof 1Nhydrochloric acid,mix with a vortex mixer,and discard the aqueous layer.Wash the organic layer twice with 2mLof 1Nhydrochloric acid,discarding the aqueous layer.To the organic layer add 2mLof water,mix with a vortex mixer,and discard the aqueous layer.Wash the organic layer twice with 2mLof water,discarding the aqueous layer.To the organic layer add about 1.0g of anhydrous sodium sulfate,and mix with a vortex mixer.Transfer 1.0mLof this solution to a 10-mLvolumetric flask,dilute with Mobile phaseto volume,mix,and filter.
Test solution Transfer about 62.5mg of Levmetamfetamine,accurately weighed,to a 25-mLvolumetric flask,dissolve in and dilute with chloroform to volume,and mix.Transfer 2.0mLof this solution to a suitable container,and proceed as directed in Resolution solutionbeginning with add 10mg of 2-naphthyl chloroformate and 2mLof chloroform.
Chromatographic system (see Chromatography á621ñ) The liquid chromatograph is equipped with a 274-nm detector and a 4.6-mm ×25-cm column that contains packing L36.The flow rate is about 1.5mLper minute.Chromatograph the Resolution solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.9for methamphetamine and 1.0for levmetamfetamine;and the resolution,R,between methamphetamine and levmetamfetamine is not less than 1.4.Chromatograph the Test solution,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Inject a volume (about 50µL)of the Test solutioninto the chromatograph,record the chromatogram,and measure the responses for the major peaks.Calculate the percentage of methamphetamine in the portion of Levmetamfetamine taken by the formula:
100rM/(rM+rL),in which rMis the methamphetamine peak response obtained from the Test solution,and rLis the peak response of levmetamfetamine obtained from the Test solution:not more than 0.1%is found.
Limit of nonvolatile residue Heat about 1.0g,accurately weighed,at 150to constant weight:the limit is not more than 0.5%.
Ordinary impurities á466ñ
Test solution: chloroform.
Standard solution: chloroform.
Eluant: a mixture of chloroform,cyclohexane,and diethylamine (5:4:1).
Limits No impurity exceeds 0.1%,and the total does not exceed 0.5%.
Organic volatile impurities,Method Iá467ñ: meets the requirements.
Solvent: 1.2Nhydrochloric acid.
Assay Transfer about 400mg of Levmetamfetamine to a suitable container,add 50.0mLof glacial acetic acid,and mix.Add two drops of crystal violet TS,and titrate with 0.1Nperchloric acid VS.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 14.92mg of C10H15N.
Auxiliary Information Staff Liaison:Daniel K.Bempong,Ph.D.,Scientist
Expert Committee:(PA2)Pharmaceutical Analysis 2
USP28NF23Page 1117Pharmacopeial Forum:Volume No.28(4)Page 1141