Bupivacaine Hydrochloride
;)
2-Piperidinecarboxamide,1-butyl-N-(2,6-dimethylphenyl)-,monohydrochloride,monohydrate,(±)-.
(±)-1-Butyl-2¢,6¢-pipecoloxylidide monohydrochloride,monohydrate [14252-80-3].
Anhydrous 324.90 [18010-40-7].
»Bupivacaine Hydrochloride contains not less than 98.5percent and not more than 101.5percent of C18H28N2O·HCl,calculated on the anhydrous basis.
Packaging and storage—
Preserve in well-closed containers.
Identification—
A:Infrared Absorption á197Sñ—
Solution—
Dissolve about 230mg in 15mLof water in a separator,add 1mLof 6Nammonium hydroxide,and extract with three 30-mLportions of chloroform.Evaporate the chloroform at room temperature with the aid of a stream of nitrogen,and dry the residue in vacuum.Add 2mLof chloroform to the residue,and dissolve.
B:
Ultraviolet Absorption á197Uñ—
Solution:
500µg per mL.
Medium:
0.1Nhydrochloric acid.
Absorptivities at 271nm,calculated on the anhydrous basis,do not differ by more than 3.0%.
C:
Dissolve about 50mg in 10mLof water in a small separator,render alkaline with 6Nammonium hydroxide,and extract with 10mLof ether:the aqueous layer responds to the tests for Chloride á191ñ.
pHá791ñ:
between 4.5and 6.0,in a solution (1in 100).
Water,Method Iá921ñ:
between 4.0%and 6.0%.
Residue on ignition á281ñ:
not more than 0.1%.
Heavy metals,Method IIá231ñ:
not more than 0.001%.
Limit of residual solvents—
Alcohol standard solution—
Pipet 2mLof dehydrated alcohol into a 100-mLvolumetric flask,dilute with water to volume,and mix.Transfer 2.0mLof this solution to a 50-mLvolumetric flask,dilute with water to volume,and mix.The resulting solution contains 0.08%of alcohol.
Isopropyl alcohol standard solution—
Pipet 2mLof isopropyl alcohol into a 1000-mLvolumetric flask,dilute with water to volume,and mix.Transfer 2.0mLof this solution to a 100-mLvolumetric flask,dilute with water to volume,and mix.The resulting solution contains 0.004%of isopropyl alcohol.
Test preparation—
Transfer 1.0g of Bupivacaine Hydrochloride,accurately weighed,to a 25-mLvolumetric flask,dilute with water to volume,and mix.
Chromatographic system—
Under typical conditions,the instrument is equipped with a flame-ionization detector and contains a 2-m ×6-mm column containing packing S3.The injection port is maintained at a temperature of about 200
,the column at about 175,the detector at about 280,and nitrogen is used as the carrier gas at a flow rate of about 40mLper minute.
,the column at about 175,the detector at about 280,and nitrogen is used as the carrier gas at a flow rate of about 40mLper minute.
Procedure—
Inject equal volumes (about 5µL)of the Test preparation,the Alcohol standard solution,and the Isopropyl alcohol standard solutionsuccessively into the gas chromatograph.Measure the responses of the alcohol peak and the isopropyl alcohol peak in each chromatogram.Determine the percentage of alcohol taken by the formula:
2(rU/rS),
and determine the percentage of isopropyl alcohol taken by the formula:
0.1(rU/rS),
in which rUand rSare the responses of the respective analytes in the Test preparationand of the corresponding analytes in the Alcohol standard solutionand the Isopropyl alcohol standard solution,respectively.The sum of the content of alcohol and the content of isopropyl alcohol does not exceed 2%.
Chromatographic purity—
Dissolve a suitable quantity of Bupivacaine Hydrochloride in a mixture of chloroform and isopropylamine (99:1)to obtain a Test solutioncontaining 20.0mg per mL.Dissolve a suitable quantity of USP Bupivacaine Hydrochloride RS,accurately weighed,in the same solvent to obtain a Standard solutioncontaining 20.0mg per mL.Quantitatively dilute a portion of this solution with the same solvent to obtain a Diluted standard solutionhaving a concentration of 100µg per mL.Apply separate 10-µLportions of the three solutions on the starting line of a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Develop the chromatogram in a suitable chamber with a solvent system consisting of a mixture of hexanes and isopropylamine (97:3)until the solvent has moved about three-fourths of the length of the plate.Remove the plate from the chamber,mark the solvent front,and dry it in warm air.Place the plate in a closed chamber with a dish containing 1g of iodine in a shallow layer,and allow to remain for about 5minutes.Remove the plate from the chamber,spray it with 7Nsulfuric acid,and examine the chromatogram:the RFvalue of the principal spot from the Test solutioncorresponds to that of the Standard solution,and the estimated size and intensity of any other spot obtained from the Test solutiondoes not exceed that of the principal spot obtained from the Diluted standard solution(0.5%);and the total of the estimated sizes and intensities of all of the other spots obtained from the Test solutiondoes not exceed four times that of the principal spot obtained from the Diluted standard solution(2.0%).
Assay—
Transfer about 600mg of Bupivacaine Hydrochloride,accurately weighed,to a 250-mLconical flask,and dissolve in 20mLof glacial acetic acid.Add 10mLof mercuric acetate TSand 3drops of crystal violet TS,and titrate with 0.1Nperchloric acid VSto a green endpoint.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 32.49mg of C18H28N2O·HCl.
Auxiliary Information—
Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 292
Pharmacopeial Forum:Volume No.30(5)Page 1589
Phone Number:1-301-816-8379