Thiethylperazine Maleate Suppositories »Thiethylperazine Maleate Suppositories contain not less than 90.0percent and not more than 110.0percent of the labeled amount of C22H29N3S2·2C4H4O4. Packaging and storage— Preserve in tight containers at temperatures below 25.Do not expose unwrapped Suppositories to sunlight. USP Reference standards á11ñ USP Thiethylperazine Maleate RS. NOTE—Throughout the following procedures,protect test or assay specimens,the Reference Standard,and solutions containing them,by conducting the procedures without delay,under subdued light,or using low-actinic glassware. Identification— A: The retention time of the thiethylperazine peak in the chromatogram of the Assay preparationcorresponds to that of the Standard preparationas obtained in the Assay. B: The RFvalue of the principal spot and its color,as visualized by the spray reagents in the chromatogram of the Test solution,corresponds to that of Standard solution Aas obtained in the test for Chromatographic purity. Uniformity of dosage units á905ñ: meet the requirements. Chromatographic purity— Diluent— Prepare a mixture of methanol,chloroform (stabilized with 0.75%alcohol),and ammonium hydroxide (55:45:1). Standard solutions— Dissolve an accurately weighed quantity of USP Thiethylperazine Maleate RSin Diluent,and mix to obtain a solution having a known concentration of about 10mg per mL.Dilute this solution quantitatively with Diluentto obtain Standard solutions,designated below by letter,having the following compositions: Standard
solution Dilution Concentration
(µg RS
per mL) Percentage (%,
for comparison
with test
specimen) A (1in 20) 500 5 B (1in 33) 300 3 C (1in 50) 200 2 D (1in 100) 100 1 E (1in 200) 50 0.5 Test solution Transfer a number of Suppositories,equivalent to about 20mg of thiethylperazine maleate,to a funnel having a fine porosity fritted disk.Add 50mLof n-pentane,macerate,and mix with a glass stirring rod,collecting the filtrate in a filter flask under reduced pressure.Rinse the stirring rod and funnel with five 10-mLportions of n-pentane,and discard the filtrate.Transfer the funnel to a separate filter flask,add three 10-mLportions of Diluent,and collect the filtrate under reduced pressure.Evaporate the filtrate to dryness,add 2.0mLof Diluent,and mix.Filter the resulting solution through a 0.45-µm filter,discarding the initial portion of the filtrate. Procedure— Equilibrate for 3hours a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture in a solvent system consisting of methylene chloride,isopropyl alcohol,methanol,and ammonium hydroxide (85:15:2:1).Remove the plate from the chamber,and allow the solvent to evaporate.Separately apply 10µLof the Test solutionand 10µLof each Standard solutionto the plate,and develop the chromatogram in a separate lined chamber in the solvent system previously described 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 allow to evaporate in a stream of nitrogen for about 10minutes.Examine the plate under short-and long-wavelength UVlight,and compare the intensities of any secondary spots observed in the chromatogram of the Test solutionwith those of the principal spots in the chromatograms of the Standard solutions.Spray the plate with Dragendorff's reagent followed by a 9%solution of hydrogen peroxide in water,and cover with a glass plate for 5minutes.Remove the glass plate,and observe under white light.Record the RFvalues and estimate the concentration of the secondary spots observed in the Test solution.No secondary spot from the chromatogram of the Test solutionobserved,using the visualization methods above,is larger or more intense than the principal spot obtained from Standard solution E(0.5%),and the sum of the intensities of the secondary spots obtained from the Test solutioncorresponds to not more than 5%. Assay— Mobile phase— Prepare a filtered and degassed mixture of methanol and 10%ammonium carbonate (9:1).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ). Diluent— Prepare a mixture of methanol,chloroform,and ammonium hydroxide (55:45:1). Standard preparation— Dissolve an accurately weighed quantity of USP Thiethylperazine Maleate RSin Diluent,and dilute quantitatively,and stepwise if necessary,with Diluentto obtain a solution having a known concentration of about 0.1mg per mL. Assay preparation— Weigh not fewer than 20Suppositories and freeze them at 0for about 30minutes.Grind the Suppositories into small particles,and transfer an accurately weighed portion of the mass,equivalent to about 10mg of thiethylperazine maleate,to a 100-mLvolumetric flask.Add about 30mLof Diluent,and gently shake for about 10minutes or until the mass dissolves.Dilute with Diluentto volume,mix,and filter through about 2g of anhydrous sodium sulfate,discarding the first portion of the filtrate. Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 265-nm detector and a 4.6-mm ×25-cm column that contains 5-µm,base-deactivated packing L1.The flow rate is about 2mLper minute,and the column temperature is maintained at 45.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the resolution,R,between the thiethylperazine peak and adjacent peaks is not less than 1.0;the column efficiency is not less than 1000theoretical plates;the tailing factor for thiethylperazine is not more than 2.5;and the relative standard deviation for replicate injections is not more than 2.0%. Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C22H29N3S2·2C4H4O4in the portion of Suppositories taken by the formula: 100C(rU/rS), in which Cis the concentration,in mg per mL,of USP Thiethylperazine Maleate RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively. Auxiliary Information— Staff Liaison:Elena Gonikberg,Ph.D.,Scientist Expert Committee:(PA4)Pharmaceutical Analysis 4 USP28–NF23Page 1910 Phone Number:1-301-816-8251