Trazodone Hydrochloride Click to View Image C19H22ClN5O·HCl 408.32
1,2,4-Triazolo[4,3-a]pyridin-3(2H)-one,2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-,monohydrochloride.
2-[3-[4-(m-Chlorophenyl)-1-piperazinyl]propyl]s-triazolo[4,3-a]-pyridin-3(2H)-one monohydrochloride [25332-39-2]. »Trazodone Hydrochloride contains not less than 97.0percent and not more than 102.0percent of C19H22ClN5O·HCl,calculated on the dried basis. Packaging and storage— Preserve in tight,light-resistant containers. USP Reference standards á11ñ USP Trazodone Hydrochloride RS. Identification— A: Infrared Absorption á197Kñ. B: 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 a pressure of about 50mm of mercury at 105for 3hours:it loses not more than 0.5%of its weight. Residue on ignition á281ñ: not more than 0.2%. Chromatographic purity— Mobile phase— Prepare a filtered and degassed mixture of 0.5%trifluoroacetic acid,tetrahydrofuran,acetonitrile,and methanol (13.5:3:3:1).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ). Standard solution— Dissolve an accurately weighed quantity of USP Trazodone Hydrochloride RSin Mobile phase,and dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having a known concentration of about 2µg per mL. System suitability solution— Dissolve suitable quantities of 3-chloroaniline and USP Trazodone Hydrochloride RSin Mobile phaseto obtain a solution containing about 0.1mg per mLof 3-chloroaniline and 0.01mg per mLof trazodone hydrochloride,respectively. Test solution— Transfer about 50mg of trazodone hydrochloride,accurately weighed,to a 50-mLvolumetric flask,dissolve in and dilute with Mobile phaseto volume,and filter. Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 248-nm detector and a 4.6-mm ×15-cm column that contains 3-µm packing L7.The flow rate is about 1.0mLper minute.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.6for 3-chloroaniline and 1for trazodone hydrochloride,and the resolution,R,between 3-chloroaniline and trazodone hydrochloride,is not less than 12.Chromatograph the Standard solution,and record the peak responses as directed for Procedure:the tailing factor for the analyte peak is not more than 2.0,and the relative standard deviation for replicate injections is not more than 5%. Procedure— Separately inject equal volumes (about 10µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the responses for all of the peaks.Calculate the percentage of each peak,other than the trazodone hydrochloride peak,in the Trazodone Hydrochloride taken by the formula: 100(CS/CT)(rU/rS), in which CSis the concentration,in mg per mL,of USP Trazodone Hydrochloride RSin the Standard solution,CTis the concentration,in mg per mL,of trazodone hydrochloride in the Test solution,rUis the response of each peak,other than the trazodone hydrochloride peak,obtained from the Test solution,and rSis the peak response for trazodone hydrochloride obtained from the Standard solution:not more than 0.4%for any single impurity and not more than 1.0%of total impurities are found. Ordinary impurities á466ñ Test solution: methanol. Standard solution: methanol. Eluant: a mixture of cyclohexane,acetone,and ammonium hydroxide (8:4.5:0.5). Visualization: 1. Assay— 0.01M Ammonium phosphate buffer— Transfer 1.15g of monobasic ammonium phosphate to a 1000-mLvolumetric flask,and dissolve in water.Add 1.0mLof 1Nsodium hydroxide,dilute with water to volume,and mix.Adjust this solution,if necessary,with either 10%phosphoric acid or 1Nsodium hydroxide to a pHof 6.0±0.1,and filter. Mobile phase— Prepare a filtered and degassed mixture of methanol and 0.01M Ammonium phosphate buffer(60:40).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ). Internal standard solution— Dissolve a suitable quantity of butylparaben in methanol to obtain a solution containing about 2mg per mL. Standard preparation— Dissolve an accurately weighed quantity of USP Trazodone Hydrochloride RSin Mobile phaseto obtain a solution having a known concentration of about 2.5mg per mL.Transfer 4.0mLof this solution to a 100-mLvolumetric flask,add 2.0mLof Internal standard solution,dilute with Mobile phaseto volume,and mix to obtain a solution having a known concentration of about 0.1mg of USP Trazodone Hydrochloride RSper mL. Assay preparation— Transfer an accurately weighed quantity of about 125mg of Trazodone Hydrochloride to a 50-mLvolumetric flask,dissolve in and dilute with Mobile phaseto volume,and mix.Transfer 4.0mLof this solution to a 100-mLvolumetric flask,add 2.0mLof the Internal standard solution,dilute with Mobile phaseto 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 L1.The flow rate is about 1.5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the resolution,R,between the trazodone and butylparaben peaks is not less than 3.0,and the relative standard deviation for replicate injections is not more than 2.0%. Procedure— Separately inject equal volumes (about 25µL)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 0.6for butylparaben and 1.0for trazodone.Calculate the quantity,in mg,of C19H22ClN5O·HCl in the portion of Trazodone Hydrochloride taken by the formula: 1250C(RU/RS), in which Cis the concentration,in mg per mL,of USP Trazodone Hydrochloride RSin the Standard preparation,and RUand RSare the ratios of the peak responses of the trazodone to the internal standard 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 1953 Phone Number:1-301-816-8330