Dextroamphetamine Sulfate Oral Solution
(Monograph under this new title—to become official June 1,2005)
(Current monograph title is Dextroamphetamine Sulfate Elixir)
»Dextroamphetamine Sulfate Oral Solution contains,in each 100mL,not less than 90.0mg and not more than 110.0mg of dextroamphetamine sulfate [(C9H13N)2·H2SO4].
Packaging and storage— Preserve in tight,light-resistant containers.
Identification— Transfer 25mLof Oral Solution to a 250-mLseparator,add 25mLof water and 5mLof 2.5Nsodium hydroxide,mix,and extract with 60mLof ether.Wash the ether extract with two 5-mLportions of 0.25Nsodium hydroxide,and discard the washings.Filter the ether extract through a pledget of cotton,previously saturated with ether,into a 100-mLbeaker,and evaporate on a steam bath in a current of air to about 1mL.Dissolve the residue in 3mLof alcohol,and transfer to a glass-stoppered,125-mLconical flask containing 25mLof water.Rinse the beaker with 3mLof alcohol,and transfer to the flask.Cool to about 15,add 3mLof 1Nsodium hydroxide,then add 1mLof a mixture of 1volume of benzoyl chloride and 2volumes of anhydrous ethyl ether,and shake for 2minutes.Filter the precipitate,wash with about 15mLof cold water,and recrystallize twice from diluted alcohol:the benzoyl derivative of dextroamphetamine so obtained,after being dried at 105for 1hour,melts between 154and 160.
Alcohol content á611ñ: between 9.0%and 11.0%of C2H5OH.
Isomeric purity— Transfer 150mLof Oral Solution to a 500-mLseparator,add 15mLof 2.5Nsodium hydroxide,and extract with one 60-mLand two 40-mLportions of ether.Wash the combined ether extracts with two 10-mLportions of 0.25Nsodium hydroxide.Wash the aqueous alkaline extracts with 20mLof ether,adding the ether washing to the combined ether extracts.Filter the ether extracts through a pledget of cotton,previously saturated with ether,into a 250-mLbeaker,rinse the cotton with a small amount of ether,and evaporate on a steam bath in a current of air to about 2mL.Dissolve the residue in 20mLof chloroform,and transfer to a separator containing 35mLof 0.1Nsulfuric acid.Complete the transfer with two additional 20-mLportions of chloroform.Shake the separator vigorously for 1minute,allow the layers to separate,and discard the chloroform.Add to the liquid in the separator 2.5g of sodium bicarbonate,preventing it from coming in contact with the mouth of the separator,and swirl until most of the bicarbonate has dissolved.By means of a 1-mLsyringe,rapidly inject 1.0mLof acetic anhydride directly into the contents of the separator.Immediately insert the stopper in the separator,and shake vigorously until the evolution of carbon dioxide has ceased,releasing the pressure as necessary through the stopcock.Allow to stand for 5minutes,and extract the solution with 50mLof chloroform,shaking vigorously for 1minute.Pass the chloroform extract through a pledget of filter cotton into a 100-mLbeaker,rinse the cotton with a small amount of chloroform,and evaporate on a steam bath in a current of air or nitrogen to dryness.Heat and triturate the residue until the odor of chloroform is no longer perceptible.Allow the residue to cool,inducing it to crystallize.Reduce the crystals to a fine powder,heat at 80for 30minutes,and cool:the specific rotation of the acetylamphetamine so obtained,determined in a solution in chloroform containing 20mg per mL,a 200-mm semimicro polarimeter tube being used,is between -37.5and -44.0.
Assay—
Chromatographic column— Proceed as directed for Column Partition Chromatographyunder Chromatography á621ñ,packing a chromatographic tube with a mixture of 2g of Solid Supportand 1mLof 0.06Nhydrochloric acid.
Standard preparation— Dissolve an accurately weighed quantity of USP Dextroamphetamine Sulfate RSin 1.8Nsulfuric acid (previously saturated with chloroform),and dilute quantitatively and stepwise with the same solvent to obtain a solution having a known concentration of about 0.5mg per mL.
Assay preparation— Pipet 5mLof Oral Solution into a 100-mLbeaker,add 1drop of 3Nhydrochloric acid,and swirl to mix.Add 6g of purified siliceous earth,and mix with a glass rod until a fluffy mixture is obtained.
Procedure— Transfer the Assay preparationto the Chromatographic column,and complete the preparation of the column.Wash the prepared column with 100mLof chloroform that previously has been saturated with water,and discard the washing.Arrange to collect the eluate in a separator containing 10.0mLof 1.8Nsulfuric acid that previously has been saturated with chloroform.Pass through the column 60mLof a freshly prepared ammoniacal chloroform solution,made by shaking 50volumes of chloroform with 1volume of ammonium hydroxide for 1to 2minutes and discarding the aqueous phase.Complete the elution with 60mLof chloroform (previously saturated with water).Shake the separator vigorously for 1minute,allow the layers to separate,and discard the chloroform.Concomitantly determine the absorbances of the Standard preparationand the Assay preparationin 1-cm cells at 280nm and at the maximum at about 257nm,with a suitable spectrophotometer,using 1.8Nsulfuric acid (previously saturated with chloroform)as the blank.Calculate the quantity,in mg,of dextroamphetamine sulfate [(C9H13N)2·H2SO4]in the portion of Oral Solution taken by the formula:
10C(A257-A280)U/(A257-A280)S,
in which Cis the concentration,in mg per mL,of USP Dextroamphetamine Sulfate RSin the Standard preparation;and the parenthetic expressions are the differences in the absorbances of the two solutions at the wavelengths indicated by the subscripts,for the Assay preparation(U)and the Standard preparation(S),respectively.
(Official June 1,2005)
Auxiliary Information— Staff Liaison:Salvador C.Salado,M.S.,Scientist and Latin American Liaison
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 608
Pharmacopeial Forum:Volume No.30(5)Page 1613
Phone Number:1-301-816-8165