Bupivacaine Hydrochloride and Epinephrine Injection
»Bupivacaine Hydrochloride and Epinephrine Injection is a sterile solution of Bupivacaine Hydrochloride and Epinephrine or Epinephrine Bitartrate in Water for Injection.It contains not less than 93.0percent and not more than 107.0percent of the labeled amount of bupivacaine hydrochloride (C18H28N2O·HCl).The content of epinephrine (C9H13NO3)does not exceed 0.001percent (1in 100,000).It contains the equivalent of not less than 90.0percent and not more than 115.0percent of the labeled amount of epinephrine (C9H13NO3).
Packaging and storage— Preserve in single-dose or in multiple-dose containers,preferably of Type Iglass,protected from light.Injection labeled to contain 0.5%or less of bupivacaine hydrochloride may be packaged in 50-mLmultiple-dose containers.
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 Epinephrine Injection.
Identification—
A: It responds to the Identificationtests under Bupivacaine Hydrochloride Injection.
B: Pipet a volume of Injection,equivalent to about 50µg of epinephrine,into a suitable container,add 0.1mLof Ferro-citrate solutionand 2.0mLof Buffer solution(prepared as directed under Epinephrine Assay á391ñ),mix,and allow the solution to stand for 10minutes.Filter the solution:the filtrate is violet in color and may turn brownish.
Bacterial endotoxins á85ñ— It contains not more than 1.6USP Endotoxin Units per mg of bupivacaine hydrochloride.
pHá791ñ: between 3.3and 5.5.
Other requirements— It meets the requirements under Injections á1ñ.
Assay for bupivacaine hydrochloride—
pH6.8Phosphate buffer ,Mobile phase,Internal standard solution,Standard preparation,Chromatographic system,and Procedure—Proceed as directed in the Assayunder Bupivacaine Hydrochloride Injection.
Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 50mg of bupivacaine hydrochloride,to a 100-mLvolumetric flask,add 10.0mLof Internal standard solution,dilute with methanol to volume,and mix.
Assay for epinephrine—
Mobile phase— Prepare a suitably filtered and degassed mixture of water,methanol,and 2Mmonobasic sodium phosphate (900:50:50),containing in each 1000mL,40mg of edetate disodium,0.4mLof phosphoric acid,and 0.4g of sodium 1-octanesulfonate.Make adjustments,if necessary,to obtain a retention time of not less than 11minutes for the epinephrine peak (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Dissolve an accurately weighed quantity of USP Epinephrine Bitartrate RSin Mobile phaseto obtain a solution having a concentration of about 2µg per mL.
Resolution solution— Dissolve suitable quantities of epinephrine bitartrate and dopamine hydrochloride in Mobile phaseto obtain a solution containing about 2µg of each per mL.
Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 25µg of epinephrine,to a 25-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with an electrochemical detector held at a potential of +0.75volt and a 4.6-mm ×25-cm column that contains packing L1.The flow rate is about 1.2mLper minute.Chromatograph the Resolution solution,and record the peak responses as directed for Procedure:the resolution,R,between the epinephrine and dopamine peaks is not less than 6.0;and the relative retention times are about 2for dopamine and 1.0for epinephrine.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in µg,of epinephrine (C9H13NO3)in each mLof the Injection taken by the formula:
(183.21/333.30)(25)(C/V)(rU/rS),
in which 183.21and 333.30are the molecular weights of epinephrine and epinephrine bitartrate,respectively;Cis the concentration,in µg per mL,of USP Epinephrine Bitartrate RSin the Standard preparation;Vis the volume,in mL,of Injection taken;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 294
Phone Number:1-301-816-8379