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 95.0 percent and not more than 105.0 percent of the labeled amount of propoxycaine hydrochloride (C16H26N2O3·HCl), not less than 95.0 percent and not more than 105.0 percent of the labeled amount of procaine hydrochloride (C13H20N2O2·HCl), and an amount of norepinephrine bitartrate (C8H11NO3·C4H6O6·H2O) equivalent to not less than 90.0 percent and not more than 110.0 percent of the labeled amount of norepinephrine (C8H11NO3).
Packaging and storage— Preserve in single-dose or in multiple-dose containers, preferably of Type I glass.
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 clarity under Norepinephrine Bitartrate Injection.
Identification—
A: Cool a mixture of 10 mL of Injection and 10 mL of 3 N hydrochloric acid in an ice bath to 0, add 5 mL of sodium nitrite solution (1 in 5), stirring gently, and 2 mL of a solution of 0.1 g of 2-naphthol in 5 mL of 1 N sodium 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 191.
C: To about 5 mL of Injection add 1 drop of ferric chloride TS: a green color develops (presence of norepinephrine bitartrate).
Bacterial endotoxins 85— It contains not more than 0.8 USP Endotoxin Unit per mg of propoxycaine hydrochloride.
pH 791: between 3.5 and 5.0.
Other requirements— It meets the requirements under Injections 1.
Assay for propoxycaine and procaine hydrochlorides—
Standard propoxycaine hydrochloride preparation— Prepare, by quantitative and stepwise dilution, a solution in 2 N hydrochloric acid containing about 50 µg of USP Propoxycaine Hydrochloride RS, accurately weighed, in each mL.
Standard procaine hydrochloride preparation— Prepare, by quantitative and stepwise dilution, a solution in 2 N hydrochloric acid containing about 200 µg of USP Procaine Hydrochloride RS, accurately weighed, in each mL.
Assay preparation— Transfer an accurately measured volume of Injection, equivalent to about 100 mg of procaine hydrochloride, to a 125-mL separator containing 25 mL of chloroform and 10 mL of water. Add 5 mL of 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-mL portions of chloroform, adding the extracts to the second separator. Extract the combined chloroform extracts with 35 mL of 2 N hydrochloric acid, transfer the chloroform to a third separator, and transfer the acid extract to a 100-mL volumetric flask. Extract the chloroform with two 10-mL portions of 2 N hydrochloric acid, add the acid extracts to the volumetric flask, dilute with 2 N hydrochloric acid to volume, and mix. Transfer 15.0 mL of this solution to a second 100-mL volumetric flask, dilute with 2 N hydrochloric acid to volume, and mix.
Procedure— Concomitantly determine the absorbances of the Standard preparations and the Assay preparation, in 1-cm cells, at 296 nm and 272 nm, with a suitable spectrophotometer, using water as the blank.
Calculate the quantity, in mg, of propoxycaine hydrochloride (C16H26N2O3·HCl) in each mL of the Injection taken by the formula:
(0.667C / V)(A296A4 A272A3) / (A1A4 A2A3)
in which C is the concentration, in µg per mL, of USP Propoxycaine Hydrochloride RS in the Standard propoxycaine hydrochloride preparation, V is the volume, in mL, of Injection taken, A1 and A2 are the absorbances of the Standard propoxycaine hydrochloride preparation at 296 nm and 272 nm, respectively, A3 and A4 are the absorbances of the Standard procaine hydrochloride preparation at 296 nm and 272 nm, respectively, and A296 and A272 are the absorbances of the Assay preparation at 296 nm and 272 nm, respectively.
Calculate the quantity, in mg, of procaine hydrochloride (C13H20N2O2·HCl) in each mL of the Injection taken by the formula:
(0.667C / V)(A272A1 A296A2) / (A1A4 A2A3)
in which C is the concentration, in µg per mL, of USP Procaine Hydrochloride RS in the Standard procaine hydrochloride preparation, and V is the volume, in mL, of Injection taken.
Change to read:
Assay for norepinephrine—
Ferro-citrate solution, Buffer solution, and Standard preparation—Prepare as directed under Epinephrine Assay 391, except to read “USP Norepinephrine Bitartrate RS” for “USP Epinephrine Bitartrate RS” throughout.
Assay preparation— Prepare as directed for Assay Preparation under Epinephrine Assay 391 except to read “norepinephrine” where “epinephrine” is specified.
Procedure— Proceed as directed for Procedure under Epinephrine Assay 391. Calculate the quantity, in mg, of norepinephrine (C8H11NO3) in each mL of the Injection taken by the formula:
(169.18 / 337.28)(0.05C / V)(AU / AS)
USP32in which 169.18 and 337.28USP32 are the molecular weights of norepinephrine and norepinephrine bitartrate monohydrate, respectively; C is the concentration, in µg per mL, USP32 of USP Norepinephrine Bitartrate RS in the Standard preparation; and V is the volume, in mL, of Injection taken.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Daniel K. Bempong, Ph.D.
Senior Scientist
1-301-816-8143		 (MDPS05) Monograph Development-Pulmonary and Steroids
Reference Standards Lili Wang, Technical Services Scientist
1-301-816-8129
RSTech@usp.org
85 Radhakrishna S Tirumalai, Ph.D.
Senior Scientist
1-301-816-8339		 (MSA05) Microbiology and Sterility Assurance
USP32–NF27 Page 3416
Pharmacopeial Forum: Volume No. 34(1) Page 110