Procaine and Tetracaine Hydrochlorides and Levonordefrin Injection
»Procaine and Tetracaine Hydrochlorides and Levonordefrin Injection is a sterile solution of Procaine Hydrochloride,Tetracaine Hydrochloride,and Levonordefrin in Water for Injection.It contains not less than 95.0percent and not more than 105.0percent of the labeled amount of procaine hydrochloride (C13H20N2O2·HCl),not less than 95.0percent and not more than 105.0percent of the labeled amount of tetracaine hydrochloride (C15H24N2O2·HCl),and not less than 90.0percent and not more than 110.0percent of the labeled amount of levonordefrin (C9H13NO3).
Packaging and storage— Preserve in single-dose or in multiple-dose containers,preferably of Type Iglass.
Labeling— The label indicates that the Injection is not to be used if its color is pinkish or darker than slightly yellow or if it contains a precipitate.
Color and clarity— Using the Injection as the Test solution,proceed as directed for Color and clarityunder Mepivacaine Hydrochloride and Levonordefrin Injection.
Identification—
A: Mix 10mLof Injection with 10mLof 3Nhydrochloric acid,cool to 0in an ice bath,add 5mLof sodium nitrite solution (1in 5),stirring gently,add 2mLof a solution of 0.1g of 2-naphthol in 5mLof 1Nsodium hydroxide,and observe immediately:a bright orange-red precipitate is formed (presence of a primary aminophenyl group).
B: It responds to the tests for Chloride á191ñ.
C: To about 25mLof Injection add 1drop of ferric chloride TS:the solution immediately turns a light green and changes to a light blue within 1minute.Add 2drops of 3Nhydrochloric acid:the color reverts to light green (presence of levonordefrin).
Bacterial endotoxins á85ñ— It contains not more than 0.6USP Endotoxin Unit per mg of procaine hydrochloride.
pHá791ñ: between 3.5and 5.0.
Other requirements— It meets the requirements under Injections á1ñ.
Assay for procaine hydrochloride— Transfer 25.0mLof Injection to a 250-mLbeaker,add 10mLof dilute hydrochloric acid (1in 2),15mLof water,and 1.0mLof formaldehyde solution,and allow to stand for 3minutes.Titrate with 0.1Msodium nitrite VS,using starch iodide paper as an external indicator.Perform a blank determination,and make any necessary correction.Calculate the quantity,in mg,of C13H20N2O2·HCl in each mLof the Injection taken by the formula:
(272.78/25)(V2M2-0.5V1M1),
in which V2is the volume,in mL,and M2is the exact molarity of the 0.1Msodium nitrite solution used in the titration,V1and M1are as defined under Assay for tetracaine hydrochloride,and 272.78is the molecular weight of procaine hydrochloride.
Assay for tetracaine hydrochloride— Transfer 50.0mLof Injection to a 100-mLbeaker,add 5g of sodium acetate and 5mLof isopropyl alcohol,and stir until the sodium acetate is dissolved.Add 1.5mLof potassium thiocyanate solution (75in 100),and stir while cooling in an ice bath.Keep in the ice bath for 1hour,stirring about four times during the period.Do not stir excessively.Prepare a filtering crucible with double suitable filter paper,connect to a suction flask,and moisten the paper with a few drops of the clear supernatant.Remove the excess liquid by suction.Filter the mixture,and dry by suction.Transfer the entire contents of the crucible to the original beaker,and rinse the crucible with 10mLof dilute hydrochloric acid (1in 2),followed by 30mLof water.Transfer the rinsings to the beaker.Cool in ice,and titrate with 0.02Msodium nitrite VS,using starch iodide paper as an external indicator.Perform a blank determination,using 10mLof dilute hydrochloric acid (1in 2)and 30mLof water,and make any necessary correction.Calculate the quantity,in mg,of C15H24N2O2·HCl in each mLof the Injection taken by the formula:
(300.83/50)(V1M1),
in which V1is the volume,in mL,and M1is the exact molarity of the 0.02Msodium nitrite used in the titration,and 300.83is the molecular weight of tetracaine hydrochloride.
Assay for levonordefrin—
Ferro-citrate solution,Buffer solution,and Standard preparation— Prepare as directed under Epinephrine Assay á391ñ.
Assay preparation— Proceed with Injection as directed for Assay Preparationunder Epinephrine Assay á391ñ,except to read “levonordefrin”where “epinephrine”is specified.
Procedure— Proceed as directed for Procedureunder Epinephrine Assay á391ñ.Calculate the quantity,in mg,of levonordefrin (C9H13NO3)in each mLof the Injection taken by the formula:
(183.21/333.30)(0.05C/V)(AU/AS),
in which 183.21and 333.30are the molecular weights of levonordefrin and epinephrine bitartrate,respectively,Cis the concentration,in µg per mL,of USP Epinephrine Bitartrate RSin the Standard preparation,and Vis the volume,in mL,of Injection taken.
Auxiliary Information— Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 1629
Phone Number:1-301-816-8379