Thiothixene Capsules
»Thiothixene Capsules contain not less than 90.0percent and not more than 110.0percent of the labeled amount of C23H29N3O2S2.
Packaging and storage— Preserve in well-closed,light-resistant containers.
Identification— Dissolve a portion of the contents of Capsules in a solvent consisting of equal volumes of chloroform and methanol to obtain a solution containing 1mg of thiothixene per mL.Shake by mechanical means for 10minutes,clarify a portion of the mixture by centrifugation,filter,if necessary,and use the clear supernatant or filtrate for the test.Apply 10µLof this test solution,10µLof a Standard solution containing 1mg of USP Thiothixene RSper mLin the same medium,and 10µLof a mixture of equal volumes of the test solution and the Standard solution to a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Allow the spots to dry,and develop the chromatogram in a solvent system consisting of a mixture of ethyl acetate,methanol,and diethylamine (65:35:5)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and locate the spots on the plate by viewing under short-and long-wavelength UVlight.Spray the plate lightly with acidified iodoplatinate spray reagent (prepared by mixing 1volume of hydrochloric acid with 50volumes of potassium iodoplatinate TS):the RFvalue of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution and the mixed test-Standard solution.
Dissolution á711ñ—
Medium— Dissolve 2.0g of sodium chloride and 7mLof hydrochloric acid in water to make 1000mL,and mix;900mL.
Apparatus 1: 100rpm.
Time: 20minutes.
Buffer solution— On the day of use,prepare a mixture of 55volumes of dibasic potassium phosphate solution (87in 1000),20volumes of citric acid monohydrate solution (21in 200),and 40volumes of sodium hydroxide solution (1in 25).
Methyl orange solution— Transfer 15.5g of boric acid and 2.0g of methyl orange to a glass-stoppered,1000-mLflask.Add 500mLof water,insert the stopper,and shake by mechanical means for not less than 3hours.Filter through retentive filter paper,and wash the filtrate with two 100-mLportions of chloroform,discarding the chloroform washings.Store the Methyl orange solutionover 50mLof chloroform in a glass-stoppered bottle.
Procedure— Prepare a Test preparationby passing a 60-mLportion of the dissolution solution through a suitable filter,discarding the first 5mLof the filtrate,and diluting the subsequent filtrate quantitatively,if necessary,to obtain a concentration of about 1µg of thiothixene per mL.Prepare a Standard preparationof USP Thiothixene RSin Dissolution Mediumhaving a known concentration of about 1µg per mL.Transfer 40.0mLeach of the Test preparation,the Standard preparation,and Dissolution Mediumto provide the blank,to individual separators,each containing 8.0mLof Buffer solution,10.0mLof Methyl orange solution,and 50.0mLof chloroform.Shake for 3minutes,allow the layers to separate,transfer 40.0mLof the chloroform layer,clarified by centrifugation,to a 60-mLseparator containing 8.0mLof dilute hydrochloric acid (1in 120),shake for 1minute,and allow the layers to separate.Concomitantly determine the absorbances of the aqueous layers in 1-cm cells,at the wavelength of maximum absorbance at about 508nm,with a suitable spectrophotometer,using the blank to set the instrument.Calculate the quantity,in µg per mL,of C23H29N3O2S2in the Test preparationtaken by the formula:
C(AU/AS),
in which Cis the concentration,in µg per mL,of USP Thiothixene RSin the Standard preparation,and AUand ASare the absorbances of the solutions from the Test preparationand the Standard preparation,respectively,and,from the known extent of dilution,determine the amount of it in the dissolution solution.
Tolerances— Not less than 80%(Q)of the labeled amount of C23H29N3O2S2is dissolved in 20minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Assay— [NOTE—Perform the dilution operations in low-actinic glassware.]
Mobile phase ,Standard preparation,and Chromatographic system—Prepare as directed in the Assayunder Thiothixene.
Assay preparation— Transfer,as completely as possible,the contents of not less than 20Capsules to a tared beaker,and weigh.Mix,and transfer an accurately weighed portion of the powder,equivalent to about 10mg of thiothixene,to a 500-mLvolumetric flask.Add about 400mLof methanol,shake by mechanical means for 10minutes,place in an ultrasonic bath for 5minutes,dilute with methanol to volume,and filter the suspension through a 5-µm polytef membrane filter.
Procedure— Proceed as directed for Procedurein the Assayunder Thiothixene.Calculate the quantity,in mg,of C23H29N3O2S2in the portion of Capsules taken by the formula:
500C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Thiothixene RSin the Standard preparation,and rUand rSare the peak responses 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 1920
Phone Number:1-301-816-8330