Thiothixene Click to View Image C23H29N3O2S2 443.63
N,N-Dimethyl-9-[3-(4-methyl-1-piperazinyl)propylidene]thioxanthene-2-sulfonamide [5591-45-7;3313-26-6]. »Thiothixene contains not less than 96.0percent and not more than 101.5percent of C23H29N3O2S2,calculated on the dried basis. Packaging and storage— Preserve in tight,light-resistant containers. USP Reference standards á11ñ USP Thiothixene RS.USP(E)-Thiothixene RS. Identification— A: Infrared Absorption á197SñSolution: 1in 20. Medium: chloroform. B: Ultraviolet Absorption á197UñSolution: 10µg per mL. Medium: methanol. Absorptivities at about 230nm and 307nm,calculated on the dried basis,do not differ by more than 4.0%. Melting range,Class Iá741ñ: between 147and 153.5. Loss on drying á731ñ Dry it in vacuum at 100for 3hours:it loses not more than 2.0%of its weight. Residue on ignition á281ñ: not more than 0.2%. Selenium á291ñ: 0.003%. Heavy metals,Method IIá231ñ: 0.0025%. Limit of (E)-thiothixene [NOTE—Prepare all solutions in low-actinic glassware.] Mobile phase— Transfer 6.9g of monobasic sodium phosphate to a 1-liter volumetric flask,dissolve in and dilute with deionized water to volume,and mix.Filter through a suitable membrane filter.Mix 4volumes of this solution with 6volumes of methanol.The concentration of methanol may be adjusted to meet the system suitability requirements. Standard preparations— A— Using accurately weighed quantities of USP(E)-Thiothixene RSand USP Thiothixene RS,prepare a solution in methanol containing,in each mL,0.4mg and 1.2mg,respectively. B— Transfer 5.0mLof Standard preparation Ato a 100-mLvolumetric flask,dilute with methanol to volume,and mix. C— Transfer about 200mg of thiothixene,accurately weighed,to a 100-mLvolumetric flask.Transfer 5.0mLof Standard preparation Ato the same flask,dissolve in and dilute with methanol to volume,and mix. Test preparation— Transfer about 200mg of Thiothixene,accurately weighed,to a 100-mLvolumetric flask.Dissolve in methanol,dilute with methanol to volume,and mix. Procedure— Concomitantly introduce equal volumes (about 20µL)of Standard preparation Cand Test preparationinto a high-pressure liquid chromatograph operated at room temperature and equipped with a suitable microsyringe or sampling valve,a column containing packing L9(typically 25cm ×4.6mm),an UVdetector capable of monitoring absorption at 254nm,and a suitable recorder.The Mobile phaseis maintained at a flow rate of about 1to 1.5mLper minute.In a suitable chromatographic system,three replicate injections of Standard preparation Bshow a resolution factor of not less than 2.2between the thiothixene and (E)-thiothixene peaks,their retention times being 13and 15minutes,and between 16and 18minutes,respectively.Calculate the quantity,in mg,of (E)-thiothixene in the portion of Thiothixene taken by the formula: 5CHU/(HC-HU), in which Cis the concentration of USP(E)-Thiothixene RS,in mg per mL,in Standard preparation A;and HCand HUare the peak responses of the (E)-thiothixene peaks corrected for the tailing of the main peak,obtained from Standard preparation Cand the Test preparation,respectively:the limit of (E)-thiothixene is 1.0%. Organic volatile impurities,Method Vá467ñ: meets the requirements. Solvent— Use dimethyl sulfoxide. Assay— [NOTE—Perform the dilution operations in low-actinic glassware.] Mobile phase— Mix 0.5mLof ethanolamine with 3780mLof methanol,mix 1400mLof this solution with 200mLof water,filter,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ). Standard preparation— Using an accurately weighed quantity of USP Thiothixene RS,prepare a solution in methanol having a known concentration of about 0.02mg per mL. Assay preparation— Transfer about 100mg of Thiothixene,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with methanol to volume,and mix.Pipet 2mLof the resulting solution into a 100-mLvolumetric flask,dilute with methanol to volume,and mix. Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×30-cm column that contains packing L3.The flow rate is about 0.5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency determined from the analyte peak is not less than 2000theoretical plates,and the relative standard deviation for replicate injections is not more than 1.5%. Procedure— Separately inject equal volumes (about 20µL)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 C23H29N3O2S2in the portion of Thiothixene taken by the formula: 5000C(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 1919 Phone Number:1-301-816-8330