Propoxycaine and Procaine Hydrochlorides and Norepinephrine Bitartrate Injection
»Propoxycaine and Procaine Hydrochlorides and Norepinephrine Bitartrate Injection is a sterile solution of Propoxycaine Hydrochloride,Procaine Hydrochloride,and Norepinephrine Bitartrate in Water for Injection.It contains not less than 95.0percent and not more than 105.0percent of the labeled amount of propoxycaine hydrochloride (C16H26N2O3·HCl),not less than 95.0percent and not more than 105.0percent of the labeled amount of procaine hydrochloride (C13H20N2O2·HCl),and an amount of norepinephrine bitartrate (C8H11NO3·C4H6O6·H2O)equivalent to not less than 90.0percent and not more than 110.0percent of the labeled amount of norepinephrine (C8H11NO3).
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 Norepinephrine Bitartrate Injection.
Identification—
A: Cool a mixture of 10mLof Injection and 10mLof 3Nhydrochloric acid in an ice bath to 0,add 5mLof sodium nitrite solution (1in 5),stirring gently,and 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 5mLof Injection add 1drop of ferric chloride TS:a green color develops (presence of norepinephrine bitartrate).
Bacterial endotoxins á85ñ— It contains not more than 0.8USP Endotoxin Unit per mg of propoxycaine hydrochloride.
pHá791ñ: between 3.5and 5.0.
Other requirements— It meets the requirements under Injections á1ñ.
Assay for propoxycaine and procaine hydrochlorides—
Standard propoxycaine hydrochloride preparation— Prepare,by quantitative and stepwise dilution,a solution in 2Nhydrochloric acid containing about 50µg of USP Propoxycaine Hydrochloride RS,accurately weighed,in each mL.
Standard procaine hydrochloride preparation— Prepare,by quantitative and stepwise dilution,a solution in 2Nhydrochloric acid containing about 200µg of USP Procaine Hydrochloride RS,accurately weighed,in each mL.
Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 100mg of procaine hydrochloride,to a 125-mLseparator containing 25mLof chloroform and 10mLof water.Add 5mLof sodium carbonate TS,shake vigorously,allow the layers to separate,and transfer the chloroform layer to a second separator.Extract the aqueous layer with two 10-mLportions of chloroform,adding the extracts to the second separator.Extract the combined chloroform extracts with 35mLof 2Nhydrochloric acid,transfer the chloroform to a third separator,and transfer the acid extract to a 100-mLvolumetric flask.Extract the chloroform with two 10-mLportions of 2Nhydrochloric acid,add the acid extracts to the volumetric flask,dilute with 2Nhydrochloric acid to volume,and mix.Transfer 15.0mLof this solution to a second 100-mLvolumetric flask,dilute with 2Nhydrochloric acid to volume,and mix.
Procedure— Concomitantly determine the absorbances of the Standard preparationsand the Assay preparation,in 1-cm cells,at 296nm and 272nm,with a suitable spectrophotometer,using water as the blank.
Calculate the quantity,in mg,of propoxycaine hydrochloride (C16H26N2O3·HCl)in each mLof the Injection taken by the formula:
(0.667C/V)(A296A4-A272A3)/(A1A4-A2A3),
in which Cis the concentration,in µg per mL,of USP Propoxycaine Hydrochloride RSin the Standard propoxycaine hydrochloride preparation,Vis the volume,in mL,of Injection taken,A1and A2are the absorbances of the Standard propoxycaine hydrochloride preparationat 296nm and 272nm,respectively,A3and A4are the absorbances of the Standard procaine hydrochloride preparationat 296nm and 272nm,respectively,and A296and A272are the absorbances of the Assay preparationat 296nm and 272nm,respectively.
Calculate the quantity,in mg,of procaine hydrochloride (C13H20N2O2·HCl)in each mLof the Injection taken by the formula:
(0.667C/V)(A272A1-A296A2)/(A1A4-A2A3),
in which Cis the concentration,in µg per mL,of USP Procaine Hydrochloride RSin the Standard procaine hydrochloride preparation,and Vis the volume,in mL,of Injection taken.
Assay for norepinephrine—
Ferro-citrate solution, Buffer solution,and Standard preparation—Prepare as directed under Epinephrine Assay á391ñ,except to read “USP Norepinephrine Bitartrate RS”for “USP Epinephrine Bitartrate RS”throughout.
Assay preparation— Prepare as directed for Assay Preparation under Epinephrine Assay á391ñexcept to read “norepinephrine”where “epinephrine”is specified.
Procedure— Proceed as directed for Procedureunder Epinephrine Assay á391ñ.Calculate the quantity,in mg,of norepinephrine (C8H11NO3)in each mLof the Injection taken by the formula:
(169.18/319.27)(0.05C/V)(AU/AS),
in which 169.18and 319.27are the molecular weights of norepinephrine and norepinephrine bitartrate,respectively,Cis the concentration,in µg per mL,calculated on the anhydrous basis,of USP Norepinephrine 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 1650
Phone Number:1-301-816-8379