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Dextroamphetamine Sulfate Tablets
» Dextroamphetamine Sulfate Tablets contain not less than 93.0 percent and not more than 107.0 percent of the labeled amount of (C9H13N)2·H2SO4.
Packaging and storage— Preserve in well-closed containers.
Identification—
A: Transfer a portion of finely ground Tablets, equivalent to about 50 mg of dextroamphetamine sulfate, to a suitable centrifuge tube. Add 25 mL of water, shake vigorously, and centrifuge until clear. Decant the clear solution into a 250-mL separator, add 5 mL of 2.5 N sodium hydroxide, and mix. Wash the ether extract with two 5-mL portions of 0.25 N sodium hydroxide, and discard the washings. Filter the ether extract through a pledget of cotton, previously saturated with ether, into a 100-mL beaker, and evaporate on a steam bath in a current of air to about 1 mL. Dissolve the residue in 3 mL of alcohol, and transfer to a glass-stoppered, 125-mL conical flask containing 25 mL of water. Rinse the beaker with 3 mL of alcohol, and transfer to the flask. Cool to about 15, add 3 mL of 1 N sodium hydroxide, then add 1 mL of a mixture of 1 volume of benzoyl chloride and 2 volumes of anhydrous ethyl ether, and shake for 2 minutes. Filter the precipitate, wash with about 15 mL of cold water, and recrystallize twice from diluted alcohol: the benzoyl derivative of dextroamphetamine so obtained, after being dried at 105 for 1 hour, melts between 154 and 160.
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution, Procedure for a Pooled Sample 711—
Medium: water; 500 mL.
Apparatus 1: 100 rpm.
Time: 45 minutes.
Determine the amount of (C9H13N)2·H2SO4 dissolved by employing the following method.
Mobile phase— Dissolve 1.1 g of sodium 1-heptanesulfonate in 575 mL of water. Add 25 mL of dilute glacial acetic acid (14 in 100) and 400 mL of methanol. Adjust by the dropwise addition of glacial acetic acid to a pH of 3.3 ± 0.1, if necessary, filter, and degas the solution. Make adjustments if necessary (see System Suitability under Chromatography 621).
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 210-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. The column temperature is maintained at 40. Chromatograph replicate injections of the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation is not more than 2.0%.
Procedure— Inject a volume (about 100 µL) of a filtered portion of the solution under test into the chromatograph, record the chromatogram, and measure the response for the major peak. Calculate the quantity of (C9H13N)2·H2SO4 dissolved in comparison with a Standard solution having a known concentration of USP Dextroamphetamine Sulfate RS in the same Medium and similarly chromatographed.
Tolerances— Not less than 75% (Q) of the labeled amount of (C9H13N)2·H2SO4 is dissolved in 45 minutes.
Uniformity of dosage units 905: meet the requirements.
Isomeric purity— Pack a pledget of fine glass wool in the base of a 200- × 25-mm chromatographic tube, with the aid of a tamping rod. Add 5 g of chromatographic siliceous earth, and tamp firmly to compress the material to a uniform mass.
Finely powder a number of Tablets, equivalent to about 300 mg of dextroamphetamine sulfate, mix the powder in a mortar with 5 g of chromatographic siliceous earth, add 1 mL of methanol and 0.5 mL of ammonium hydroxide, and triturate to a uniform mixture. Transfer the mixture without delay to the chromatographic tube, and tamp as before. Wipe the mortar and pestle with a small amount of glass wool, and insert it into the tube on top of the column. Arrange a 125-mL separator containing 35 mL of 0.1 N sulfuric acid to receive the effluent. Pass 60 mL of chloroform through the column. Shake the separator vigorously for 1 minute, allow the layers to separate, and discard the chloroform. With the aqueous phase in the separator, preventing it from coming in contact with the mouth of the separator, swirl until most of the bicarbonate has dissolved. By means of a 1-mL syringe, rapidly inject 1.0 mL of 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 5 minutes, and extract the solution with 50 mL of chloroform, shaking vigorously for 1 minute. Filter the chloroform extract through a pledget of filter cotton into a 100-mL beaker, 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 80 for 30 minutes, and cool: the specific rotation of the acetylamphetamine so obtained, determined in a solution in chloroform containing 20 mg per mL, a 200-mm semimicro polarimeter tube being used, is between 37.5 and 44.0.
Residual solvents 467: meet the requirements.
(Official January 1, 2007)
Assay—
Mobile phase— Dissolve 1.1 g of sodium 1-heptanesulfonate in 525 mL of water. Add 25 mL of dilute glacial acetic acid (14 in 100) and 450 mL of methanol. Adjust dropwise, if necessary, with glacial acetic acid to a pH of 3.3 ± 0.1. Filter through a 0.5-µm membrane filter. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Dextroamphetamine Sulfate RS in 0.12 N phosphoric acid to obtain a solution having a known concentration of about 0.3 mg per mL.
Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the mixed powder, equivalent to about 15 mg of dextroamphetamine sulfate, to a 50-mL volumetric flask. Add 40 mL of 0.12 N phosphoric acid, and sonicate for 15 minutes. Dilute with 0.12 N phosphoric acid to volume, and mix. Filter through a 0.5-µm membrane filter, discarding the first 20 mL of the filtrate.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph replicate injections of the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is not more than 3, and the relative standard deviation is not more than 2.0%.
Procedure— Separately inject equal volumes (about 50 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of (C9H13N)2· H2SO4 in the portion of Tablets taken by the formula:
50C(rU / rS),
in which C is the concentration, in mg per mL, of USP Dextroamphetamine Sulfate RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Ravi Ravichandran, Ph.D., Senior Scientist
Expert Committee : (MDPP05) Monograph Development-Psychiatrics and Psychoactives
USP29–NF24 Page 664
Pharmacopeial Forum : Volume No. 30(1) Page 94
Phone Number : 1-301-816-8330