Butorphanol Tartrate Injection
»Butorphanol Tartrate Injection is a sterile solution of Butorphanol Tartrate in Water for Injection.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of C21H29NO2·C4H6O6.It may contain a suitable preservative and a buffer.
Packaging and storage— Preserve in single-dose or in multiple-dose containers,preferably of Type Iglass,protected from light.
Identification— Apply 10-µLportions of the Injection and a Standard solution of USP Butorphanol Tartrate RShaving the same concentration about 2cm apart to a line parallel to and about 2cm from the bottom of a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Place the plate in a developing chamber containing a mixture of chloroform,ethyl acetate,and methanol (40:10:9),and develop the chromatogram until the solvent front has moved about 10cm above the line of application.Remove the plate,mark the solvent front,and allow the solvent to evaporate.Examine the plate under short-wavelength UVlight:the RFvalue of the principal spot obtained from the solution under test corresponds to that obtained from the Standard solution.Benzethonium chloride,if present,is observed as a streaked zone near the point of application.Visualize the butorphanol spots by lightly spraying the plate with a 1in 250solution of bromocresol purple in dehydrated alcohol:butorphanol appears as a blue spot against a light yellow background.
pHá791ñ: between 3.0and 5.5.
Bacterial endotoxins á85ñ— It contains not more than 88.0USP Endotoxin Units per mg of butorphanol tartrate.
Other requirements— It meets the requirements under Injections á1ñ.
Assay—
Mobile phase— Prepare a mixture of 0.05Mammonium acetate and acetonitrile (3:1)adjusted by the addition of glacial acetic acid to a pHof 4.1.The mixture is appropriately filtered and degassed.
Internal standard solution— Dissolve about 50mg of propylparaben in 5.0mLof methanol contained in a 250-mLvolumetric flask.Add water to volume,and mix.
Standard preparation— Transfer about 50mg of USP Butorphanol Tartrate RS,accurately weighed,to a 25-mLvolumetric flask containing 1.0mLof 1Nsulfuric acid.Swirl the flask to dissolve the powder completely,add water to volume,and mix.Pipet 5mLof the resulting solution into a 50-mLvolumetric flask containing 10.0mLof Internal standard solution.Add water to volume,mix,and filter through a microporous filter,discarding the first 5mLof the filtrate and collecting the remainder in a suitable container.
Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 10mg of butorphanol tartrate,to a 50-mLvolumetric flask.Add 10.0mLof Internal standard solution,mix,add water to volume,and mix.Filter through a microporous filter,discarding the first 5mLof the filtrate and collecting the remainder in a suitable container.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 280-nm detector and a 4-mm ×30-cm column that contains packing L11.The flow rate is about 2mLper minute.Chromatograph five replicate injections of the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation is not more than 1.5%,and the capacity factor for butorphanol tartrate is not less than 2.0.
Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,adjusting the flow rate and other operating parameters,if necessary,until satisfactory chromatography and peak responses are obtained.Record the chromatograms,and measure the responses for the major peaks.The relative retention times are about 1.7for propylparaben and 1.0for butorphanol tartrate.Calculate the quantity,in mg,of C21H29NO2·C4H6O6in each mLof the Injection taken by the formula:
50(C/V)(RU/RS),
in which Cis the concentration,in mg per mL,of USP Butorphanol Tartrate RSin the Standard preparation;Vis the volume,in mL,of Injection taken;and RUand RSare the peak response ratios of the butorphanol tartrate peak and the internal standard peak obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA2)Pharmaceutical Analysis 2
USP28–NF23Page 311
Phone Number:1-301-816-8139