Lidocaine Hydrochloride
C14H22N2O·HCl·H2O
288.81
Acetamide,2-(diethylamino)-N-(2,6-dimethylphenyl)-,monohydrochloride,monohydrate.
2-(Diethylamino)-2¢,6¢-acetoxylidide monohydrochloride monohydrate [6108-05-0].
Anhydrous 270.80 [73-78-9].
»Lidocaine Hydrochloride contains not less than 97.5percent and not more than 102.5percent of C14H22N2O·HCl,calculated on the anhydrous basis.
Packaging and storage—
Preserve in well-closed containers.
Labeling—
Where it is intended for use in preparing injectable dosage forms,the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms.
Identification—
A:
Dissolve about 300mg in 5to 10mLof water in a separator,add 4mLof 6Nammonium hydroxide,and extract with four 15-mLportions of chloroform.Combine the chloroform extracts,evaporate with the aid of a current of warm air,and dry the residue in vacuum over silica gel for 24hours:the crystalline precipitate so obtained responds to the Identificationtests under Lidocaine.
B:
Its solutions respond to the tests for Chloride á191ñ.
Water,Method Iá921ñ:
between 5.0%and 7.0%.
Residue on ignition á281ñ:
not more than 0.1%.
Sulfate—
Dissolve about 200mg in 20mLof water,add 2mLof 3Nhydrochloric acid,mix,and divide into two parts.To one part of the solution add 1mLof barium chloride TS:no more turbidity is produced than is present in the remaining portion of the solution to which nothing has been added.
Heavy metals,Method Iá231ñ:
0.002%.
Other requirements—
Where the label states that Lidocaine Hydrochloride is sterile,it meets the requirements for Sterility Tests á71ñand for Bacterial endotoxinsunder Lidocaine Hydrochloride Injection.Where the label states that Lidocaine Hydrochloride must be subjected to further processing during the preparation of injectable dosage forms,it meets the requirements for Bacterial endotoxinsunder Lidocaine Hydrochloride Injection.
Assay—
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 about 100mg of Lidocaine Hydrochloride,accurately weighed,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 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 20
and 25,maintained 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 the lidocaine and methylparaben peaks is not less than 3.0.
and 25,maintained 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 the lidocaine and methylparaben peaks 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 the portion of Lidocaine Hydrochloride taken by the formula:
(270.80/234.34)(50C)(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,and rUand rSare the lidocaine 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 1130
Pharmacopeial Forum:Volume No.30(4)Page 1256
Phone Number:1-301-816-8379