Alprazolam Tablets
»Alprazolam Tablets contain not less than 90.0percent and not more than 110.0percent of the labeled amount of alprazolam (C17H13ClN4).
Packaging and storage— Preserve in tight,light-resistant containers,and store at controlled room temperature.
Identification— Dissolve an amount of finely powdered Tablets,equivalent to about 15mg of alprazolam,in 10mLof sodium carbonate solution (1in 100).Add 15mLof chloroform,and shake vigorously for 30minutes.Centrifuge,withdraw the aqueous layer,and transfer the chloroform to a clean container.Add about 200mg of potassium bromide.Evaporate the chloroform from this mixture to dryness,and dry the dispersion in vacuum at 60for 24hours.Grind this dispersion into a fine powder.Prepare a suitable pellet for testing by placing about 100mg of dried potassium bromide into a die.Sprinkle about 20mg of the finely ground,alprazolam-potassium bromide dispersion onto the dried potassium bromide layer,and cover with another specimen of about 100mg of dried potassium bromide:the IRabsorption spectrum of the potassium bromide dispersion so obtained exhibits maxima characteristic of alprazolam,as compared to that of a similar preparation of USP Alprazolam RS,at the following wavenumbers:at 1609,1578,1566,1539,1530,1487,1445,1428,1379,1337,and 1320wavenumbers in the region of 1650to 1300cm-1;at 970,932,891,826,797,779,746,696,669,658,and 640wavenumbers in the region of 975to 600cm-1.
Dissolution,Procedure for a Pooled Sample á711ñ—
Buffer stock solution— Dissolve 160g of monobasic potassium phosphate and 40g of dibasic potassium phosphate in water,and dilute with water to obtain 2.0Lof solution.Add,with mixing,phosphoric acid or potassium hydroxide solution (45in 100),as necessary to adjust the solution such that,when this Buffer stock solutionis diluted 1in 10with water,the resulting solution has a pHof 6.0±0.1.
Buffer solution— Prepare a 1in 10dilution of Buffer stock solutionin water to obtain a Working buffer solutionhaving a pHof 6.0±0.1.
Medium:Buffer solution; 500mL.
Apparatus 1: 100rpm.
Time: 30minutes.
Determine the amount of C17H13ClN4dissolved employing the following method.
Mobile phase— Prepare a degassed and filtered solution of Buffer solution,acetonitrile,and tetrahydrofuran (60:35:5).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard stock solution— Prepare a solution in methanol of USP Alprazolam RShaving a known concentration of about 0.05mg per mL.
Standard solution— Add 50mLof Buffer stock solutionand 250mLof water to a 500-mLvolumetric flask.Add to the flask 5.0mLof Standard stock solutionfor every 0.25mg of alprazolam contained in the Tablet being assayed.Dilute with water to volume,and mix.
Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm ×10-cm analytical column that contains packing L7.The flow rate is about 1mLper minute.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the column efficiency is not less than 500theoretical plates,and the relative standard deviation for replicate injections is not more than 3.0%.
Procedure— Separately inject equal volumes of a filtered portion of the solution under test and the Standard solutioninto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity of C17H13ClN4dissolved based on the peak responses obtained from the solution under test and the Standard solution.
Tolerances— Not less than 80%(Q)of the labeled amount of C17H13ClN4is dissolved in 30minutes.
Uniformity of dosage units á905ñ: meet the requirements for Content Uniformity.
PROCEDURE FOR CONTENT UNIFORMITY—
Mobile phase— Prepare as directed in the Assayunder Alprazolam.
Internal standard solution— Prepare a solution of triazolam in acetonitrile having a concentration of about 0.032mg per mL.
Test preparation— Transfer 1Tablet to a container.Add about 0.4mLof water directly onto the Tablet,allow the Tablet to stand for 2minutes,and then swirl the container to disperse the Tablet.For every 0.25mg of alprazolam contained in the Tablet,add 10.0mLof Internal standard solutionto the container.Shake,and centrifuge if necessary.
Standard preparation— Prepare a solution in Internal standard solutionof USP Alprazolam RShaving a known concentration of about 0.025mg per mL.
Chromatographic system andProcedure— Proceed as directed in the Assayunder Alprazolam.Calculate the quantity,in mg,of C17H13ClN4in the Tablet by the formula:
CV(RU/RS),
where Vis the volume,in mL,of Internal standard solutionin the Test preparation;and the other terms are as defined in the Procedurefor Alprazolam.
Assay—
Mobile phase,Chromatographic system,Internal standard solution,and Standard preparation— Prepare as directed in the Assayunder Alprazolam.
Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed quantity of the powder,equivalent to about 5mg of alprazolam,to a 200-mLvolumetric flask.Transfer 2mLof water and 20mLof Internal standard solution,shake vigorously for 10minutes,dilute with acetonitrile to volume,and mix.
Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the area responses for the major peaks.Calculate the quantity,in mg,of alprazolam (C17H13ClN4)in the portion of Tablets taken by the formula:
200C(RU/RS),
in which Cis the concentration,in mg per mL,of USP Alprazolam RSin the Standard preparation;and RUand RSare the peak response ratios of the alprazolam peak relative to the internal standard peak obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Ravi Ravichandran,Ph.D.,Senior Scientist
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 70
Pharmacopeial Forum:Volume No.30(5)Page 1582
Phone Number:1-301-816-8330