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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--[(methylamino)methyl]benzyl alcohol (+)-tartrate (1:1) salt [51-42-3].
» Epinephrine Bitartrate contains not less than 97.0 percent and not more than 102.0 percent of C9H13NO3·C4H6O6, calculated on the dried basis.
Packaging and storage— Preserve in tight, light-resistant containers.
Identification— Dissolve about 500 mg in 20 mL of water containing about 100 mg of sodium bisulfite. Add 6 N ammonium hydroxide until the solution has a distinct odor of ammonia, and allow to stand in a refrigerator for 1 hour. Filter the precipitate, wash it with three 2-mL portions of cold water, then with 5 mL of cold alcohol, and finally with 5 mL of cold ether, and dry in vacuum over silica gel for 3 hours. The epinephrine so obtained responds to the Identification test under Epinephrine, and its specific rotation (see Optical Rotation 781), determined by dissolving 200 mg, accurately weighed, in sufficient dilute hydrochloric acid (1 in 20) to make 10.0 mL, is between –50 and –53.5.
Melting range 741: between 147 and 152, with decomposition.
Loss on drying 731— Dry it in vacuum over silica gel for 3 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: negligible, from 100 mg.
Limit of adrenalone— Its absorptivity (see Spectrophotometry and Light-scattering 851) at 310 nm, determined in a solution in dilute hydrochloric acid (1 in 200) containing 4 mg 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 RS containing about 200 mg per mL to obtain a solution having a known concentration of about 20 mg per mL.
Norepinephrine standard solution— Dilute with methanol an accurately measured volume of an aqueous solution of USP Norepinephrine Bitartrate RS containing 8.0 mg per mL to obtain a solution having a known concentration of 0.80 mg per mL.
Test solution— Dissolve 200 mg of Epinephrine Bitartrate in 1.0 mL of water, dilute with methanol to 10.0 mL, and mix.
Procedure— Apply 5-µL portions of Epinephrine standard solution, Norepinephrine standard solution, and Test solution to a suitable thin-layer chromatographic plate (see Chromatography 621) 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 (1 to 10): the RF value of the principal spot obtained from the Test solution corresponds to that obtained from the Epinephrine standard solution. Any spot obtained from the Test solution is not larger nor more intense than the spot with the same RF value obtained from Norepinephrine standard solution, corresponding to not more than 4.0% of norepinephrine bitartrate.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay— Dissolve about 500 mg of Epinephrine Bitartrate, accurately weighed, in 20 mL of glacial acetic acid, warming slightly if necessary to effect solution. Add crystal violet TS, and titrate with 0.1 N perchloric acid VS. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 33.33 mg of C9H13NO3·C4H6O6.
Auxiliary Information— Staff Liaison : Daniel K. Bempong, Ph.D., Scientist
Expert Committee : (MDPS05) Monograph Development-Pulmonary and Steroids
USP29–NF24 Page 809
Phone Number : 1-301-816-8143