Thiotepa Click to View Image C6H12N3PS 189.22
Tris(1-aziridinyl)phosphine sulfide [52-24-4]. »Thiotepa contains not less than 97.0percent and not more than 102.0percent of C6H12N3PS,calculated on the anhydrous basis. Caution—Great care should be taken to prevent inhaling particles of Thiotepa or exposing the skin to it. Packaging and storage— Preserve in tight,light-resistant containers,and store in a refrigerator. USP Reference standards á11ñ USP Thiotepa RS. Identification,Infrared Absorption á197Sñ Solution: 3in 400. Medium: carbon disulfide. Melting range á741ñ: between 52and 57. Water,Method Iá921ñ: not more than 2.0%. Assay— Mobile phase— Prepare a suitable filtered and degassed mixture of water and acetonitrile (9:1).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ). Standard preparation— Dissolve an accurately weighed quantity of USP Thiotepa RSin Mobile phaseto obtain a solution having a known concentration of about 1.5mg per mL. Assay preparation— Transfer about 75mg of Thiotepa,accurately weighed,to a 50-mLvolumetric flask,dissolve in Mobile phase,dilute with Mobile phaseto volume,and mix. Resolution solution— Transfer about 10mg of USP Thiotepa RSto a 4-mLvial,add 2mLof methanol,and mix.Add 50µLof 0.1%phosphoric acid solution.Place a cap on the vial,and heat at 65for 50seconds.Cool the solution,add 1mLof methanol,and mix. Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 215-nm detector and a 4-mm ×15-cm column that contains packing L1.The flow rate is about 0.8mLper minute.Chromatograph the Resolution solution,and record the peak responses as directed for Procedure:the relative retention times are about 1.25for methoxythiotepa and 1.0for thiotepa,and the resolution,R,between the methoxythiotepa peak and the thiotepa peak is not less than 3.0.Chromatograph the Standard preparation,and record the responses as directed for Procedure:the tailing factor for the thiotepa peak is not more than 1.8,the column efficiency is not less than 2600theoretical plates,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 C6H12N3PSin the portion of Thiotepa taken by the formula: 50C(rU/rS), in which Cis the concentration,in mg per mL,of USP Thiotepa RSin the Standard preparation,and rUand rSare the thiotepa peak responses obtained from the Assay preparationand the Standard preparation,respectively. Auxiliary Information— Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist Expert Committee:(PA6)Pharmaceutical Analysis 6 USP28–NF23Page 1918 Phone Number:1-301-816-8389