Temazepam Click to View Image C16H13ClN2O2 300.74
7-Chloro-1,3-dihydro-3-hydroxy-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one [846-50-4]. »Temazepam contains not less than 98.0percent and not more than 102.0percent of C16H13ClN2O2,calculated on the dried basis. Caution—Temazepam is a potent sedative:its powder should not be inhaled. Packaging and storage— Preserve in well-closed,light-resistant containers. USP Reference standards á11ñ USP Temazepam RS. Identification— A: The IRabsorption spectrum of a potassium bromide dispersion of it,previously dried,exhibits maxima only at the same wavelengths as that of a similar preparation of USP Temazepam RS. B: The UVabsorption spectrum of a 1in 80,000solution in methanol exhibits maxima and minima at the same wavelengths as that of a similar solution of USP Temazepam RS,concomitantly measured. C: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that of the Standard preparation,both relative to the internal standard,as obtained in the Assay. Loss on drying á731ñ Dry it at 105for 2hours;it loses not more than 0.5%of its weight. Residue on ignition á281ñ: not more than 0.1%. Heavy metals,Method IIá231ñ: 20ppm. Chromatographic purity— Standard stock solution— Dissolve an accurately weighed quantity of USP Temazepam RSin chloroform,and dilute quantitatively and stepwise with chloroform to obtain a solution having a known concentration of about 10mg per mL. Standard solutions Aand B— Dilute accurately measured volumes of Standard stock solutionquantitatively with chloroform to obtain Standard solutions Aand Bhaving known concentrations of about 0.1and 0.05mg per mL,respectively. Test solution— Transfer about 100mg of Temazepam,accurately weighed,to a 10-mLvolumetric flask,add chloroform to volume,and mix. Procedure— Separately apply 10µLof the Test solutionand 10µLof each Standard solutionto a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Position the plate in a chromatographic chamber,and develop the chromatograms in a solvent system consisting of cyclohexane,chloroform,methanol,and ammonium hydroxide (50:40:12:1)until the solvent front has moved about 10cm above the point of application.Remove the plate from the developing chamber,mark the solvent front,and allow the solvent to evaporate.Examine the plate under short-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:no secondary spot obtained from the Test solutionis greater in intensity than 1.0%,and the sum of the intensities of secondary spots obtained from the test solution corresponds to not more than 2.0%. Assay— Buffer solution— Dissolve 5.444g of monobasic potassium phosphate in 2000mLof water.Adjust with phosphoric acid to a pHof 3.0. Mobile phase— Prepare a filtered and degassed mixture of Buffer solutionand acetonitrile (53:47).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ). Internal standard solution— Dissolve an accurately weighed quantity of benzophenone in a mixture of methanol and water (9:1),and dilute quantitatively and stepwise with the same solvent to obtain a solution having a concentration of 0.2mg per mL. Standard preparation— Dissolve an accurately weighed quantity of USP Temazepam RSin Internal standard solutionto obtain a solution having a known concentration of 0.2mg per mL. Assay preparation— Transfer about 40.0mg of temazepam,accurately weighed,to a 200-mLvolumetric flask,add about 150mLof Internal standard solution,mix,and dilute with Internal standard solutionto volume. Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 4-mm ×25-cm column that contains packing L16.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency is not less than 800theoretical plates;the tailing factor is not more than 2;the resolution between the temazepam peak and any other peak is not less than 1,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.The relative retention times are about 1.0for temazepam and 2.0for benzophenone.Calculate the quantity,in mg,of C16H13O2N2Cl in the portion of Temazepam taken by the formula: 200C(RU/RS), in which Cis the concentration,in mg per mL,of USP Temazepam RSin the Standard preparation,and RUand RSare the peak response ratios obtained from the Assay preparationand the Standard preparation,respectively. Auxiliary Information— Staff Liaison:Salvador C.Salado,M.S.,Scientist and Latin American Liaison Expert Committee:(PA3)Pharmaceutical Analysis 3 USP28–NF23Page 1866 Phone Number:1-301-816-8165