Epinephrine Bitartrate
C9H13NO3·C4H6O6 333.29

1,2-Benzenediol,4-[1-hydroxy-2-(methylamino)ethyl]-,(R)-,[R-(R*,R*)]-2,3-dihydroxybutanedioate (1:1)(salt).
(-)-3,4-Dihydroxy-a-[(methylamino)methyl]benzyl alcohol (+)-tartrate (1:1)salt [51-42-3].
»Epinephrine Bitartrate contains not less than 97.0percent and not more than 102.0percent of C9H13NO3·C4H6O6,calculated on the dried basis.
Packaging and storage— Preserve in tight,light-resistant containers.
Identification— Dissolve about 500mg in 20mLof water containing about 100mg of sodium bisulfite.Add 6Nammonium hydroxide until the solution has a distinct odor of ammonia,and allow to stand in a refrigerator for 1hour.Filter the precipitate,wash it with three 2-mLportions of cold water,then with 5mLof cold alcohol,and finally with 5mLof cold ether,and dry in vacuum over silica gel for 3hours.The epinephrine so obtained responds to the Identificationtest under Epinephrine,and its specific rotation (see Optical Rotation á781ñ),determined by dissolving 200mg,accurately weighed,in sufficient dilute hydrochloric acid (1in 20)to make 10.0mL,is between –50and –53.5.
Melting range á741ñ: between 147and 152,with decomposition.
Loss on drying á731ñ— Dry it in vacuum over silica gel for 3hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ: negligible,from 100mg.
Limit of adrenalone— Its absorptivity (see Spectrophotometry and Light-scattering á851ñ)at 310nm,determined in a solution in dilute hydrochloric acid (1in 200)containing 4mg per mL,is not more than 0.2.
Limit of norepinephrine bitartrate—
Epinephrine standard solution— Dilute with methanol an accurately measured volume of an aqueous solution of USP Epinephrine Bitartrate RScontaining about 200mg per mLto obtain a solution having a known concentration of about 20mg per mL.
Norepinephrine standard solution— Dilute with methanol an accurately measured volume of an aqueous solution of USP Norepinephrine Bitartrate RScontaining 8.0mg per mLto obtain a solution having a known concentration of 0.80mg per mL.
Test solution— Dissolve 200mg of Epinephrine Bitartrate in 1.0mLof water,dilute with methanol to 10.0mL,and mix.
Procedure— Apply 5-µLportions of Epinephrine standard solution,Norepinephrine standard solution,and Test solutionto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Allow the spots to dry,and develop the chromatogram in an unsaturated tank using a solvent system consisting of n-butanol,water,and formic acid (7:2:1)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the solvent to evaporate in warm circulating air.Spray with Folin-Ciocalteu Phenol TS,followed by sodium carbonate solution (1to 10):the RFvalue of the principal spot obtained from the Test solutioncorresponds to that obtained from the Epinephrine standard solution.Any spot obtained from the Test solutionis not larger nor more intense than the spot with the same RFvalue obtained from Norepinephrine standard solution,corresponding to not more than 4.0%of norepinephrine bitartrate.
Assay— Dissolve about 500mg of Epinephrine Bitartrate,accurately weighed,in 20mLof glacial acetic acid,warming slightly if necessary to effect solution.Add crystal violet TS,and titrate with 0.1Nperchloric acid VS.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 33.33mg of C9H13NO3·C4H6O6.
Auxiliary Information— Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 742
Phone Number:1-301-816-8379