Lidocaine Hydrochloride and Epinephrine Injection
»Lidocaine and Epinephrine Injection is a sterile solution prepared from Lidocaine Hydrochloride and Epinephrine with the aid of Hydrochloric Acid in Water for Injection,or a sterile solution prepared from Lidocaine and Epinephrine with the aid of Hydrochloric Acid in Water for Injection,or a sterile solution of Lidocaine Hydrochloride and Epinephrine Bitartrate in Water for Injection.The content of epinephrine does not exceed 0.002percent (1in 50,000).Lidocaine and Epinephrine Injection contains the equivalent of not less than 95.0percent and not more than 105.0percent of the labeled amount of lidocaine hydrochloride (C14H22N2O·HCl)and 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,light-resistant 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 Epinephrine Injection.
Bacterial endotoxins á85ñ— It contains not more than 0.7USP Endotoxin Unit per mg of lidocaine hydrochloride.
pHá791ñ: between 3.3and 5.5.
Other requirements— It responds to the Identificationtest under Lidocaine Hydrochloride Injection.It meets also the requirements under Injections á1ñ.
Assay for lidocaine hydrochloride—
Mobile phase— Mix 50mLof glacial acetic acid and 930mLof water,and adjust with 1Nsodium hydroxide to a pHof 3.40.Mix about 4volumes of this solution with 1volume of acetonitrile,such that the retention time of lidocaine is about 4to 6minutes.Filter through a membrane filter (1µm or finer porosity),and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Dissolve about 85mg of USP Lidocaine RS,accurately weighed,with warming if necessary,in 0.5mLof 1Nhydrochloric acid in a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix to obtain a Standard preparationhaving a known concentration of about 1.7mg of lidocaine per mL.
Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 100mg of lidocaine hydrochloride,to a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Resolution preparation— Prepare a solution of methylparaben in Mobile phasecontaining about 220µg per mL.Mix 2mLof this solution and 20mLof the Standard preparation.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 30-cm ×3.9-mm column that contains packing L1and is operated at a temperature between 20and 25maintained at ±1.0of the selected temperature.The flow rate is about 1.5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 1.5%.Chromatograph about 20µLof the Resolution preparation,and record the peak responses as directed for Procedure:the resolution,R,between lidocaine and methylparaben is not less than 3.0.
Procedure— Separately inject equal volumes (about 20µL)of the Assay preparationand the Standard preparationinto the chromatograph.Record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C14H22N2O·HCl in each mLof the Injection taken by the formula:
(270.80/234.34)(50)(C/V)(rU/rS),
in which 270.80and 234.34are the molecular weights of lidocaine hydrochloride and lidocaine,respectively,Cis the concentration,in mg per mL,of USP Lidocaine RSin the Standard preparation,Vis the volume,in mL,of Injection taken,and rUand rSare the lidocaine peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Assay for epinephrine—
Mobile phase— Mix 50mLof glacial acetic acid and 930mLof water,and adjust with 1Nsodium hydroxide to a pHof 3.40.Dissolve 1.1g of sodium 1-heptanesulfonate in this solution,add 1.0mLof 0.1Medetate disodium,and mix.Mix about 9volumes of this solution with 1volume of methanol,such that the retention time of epinephrine is about 4to 6minutes.Filter through a membrane filter (1µm or finer porosity),and degas.
Standard preparation— Dissolve an accurately weighed quantity of USP Epinephrine Bitartrate RSin Mobile phaseto obtain a solution having a known concentration of about 9µg of epinephrine bitartrate per mL.Pipet 10mLof this solution into a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix to obtain a Standard preparationhaving a known concentration of about 1.8µg of epinephrine bitartrate per mL.
Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 50µg of epinephrine,to a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is fitted with a 3.9-mm ×30-cm stainless steel column packed with packing L1and is equipped with an electrochemical detector held at a potential of +650mV,a controller capable of regulating the background current,and a suitable recorder,and it is operated at a temperature between 20and 25maintained at ±1.0of the selected temperature.The flow rate is about 1mLper minute.Chromatograph the Standard preparationas directed for Procedure:the relative standard deviation of the peak responses of successive injections of the Standard preparationis not more than 1.5%.
Procedure— Separately inject equal volumes (about 20µL)of the Assay preparationand the Standard preparationinto the chromatograph by means of a suitable microsyringe or sampling valve,adjusting the specimen size and other operating parameters such that satisfactory chromatography and peak responses are obtained.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)(50)(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 1132
Pharmacopeial Forum:Volume No.30(4)Page 1257
Phone Number:1-301-816-8379