Bupivacaine Hydrochloride

Percentage (%, for C18H28N2O · HCl · H2O 342.90 Concentration comparison 2-Piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)-, Standard (μg of RS with test specimonohydrochloride, monohydrate, (±)-. solution Dilution per mL) men) (±)-1-Butyl-2′,6′-pipecoloxylidide monohydrochloride, monohy1 undiluted 160 0.8 drate [73360-54-0]. 2 3 in 4 120 0.6 Anhydrous 324.90 [18010-40-7]. 3 1 in 2 80 0.4 » Bupivacaine Hydrochloride contains not less 4 1 in 4 40 0.2 than 98.5 percent and not more than 101.5 per5 1 in 8 20 0.1 cent of C 18H28N2O · HCl, calculated on the anhyStandard solution 6—Dissolve an accurately weighed quantity drous basis. of USP Bumetanide Related Compound A RS in methanol, and dilute quantitatively, and stepwise if necessar y, with methanol Packaging and storage—Preserve in well-closed containers. to obtain a solution having a known concentration of about USP Reference standards 〈11〉— 0.04 mg per mL. USP Bupivacaine Hydrochloride RS Application volume: 25 μL. Identification— Developing solvent system: a mixture of chloroform, cycloA: Infrared Absorption 〈197S〉— hexane, glacial acetic acid, and methanol (80:10:10:2.5). Solution—Dissolve about 230 mg in 15 mL of water in a Procedure—Proceed as directed for Thin-Layer Chromatograseparator, add 1 mL of 6 N ammonium hydroxide, and extract phy under Chromatography 〈621〉. Examine the plate under with three 30-mL portions of chloroform. Evaporate the chloroshort-wavelength UV light. Any secondar y spot obtained from form at room temperature with the aid of a stream of nitrogen, the chromatogram of the Test solution having an RF value correand dry the residue in vacuum. Add 2 mL of chloroform to the sponding to the RF value of the principal spot obtained from residue, and dissolve. the chromatogram of Standard solution 6 is not larger or more intense than the principal spot obtained from the chromatoB: Ultraviolet Absorption 〈197U〉— gram of Standard solution 6: not more than 0.2% of bumetaSolution: 500 μg per mL. nide related compound A is found. For all other secondar y Medium: 0.1 N hydrochloric acid. spots obtained from the chromatogram of the Test solution, Absorptivities at 271 nm, calculated on the anhydrous basis, compare the intensity of each spot with the principal spots obdo not differ by more than 3.0%. tained from the chromatograms of Standard solutions 1 through C: Dissolve about 50 mg in 10 mL of water in a small 5: not more than 0.2% of any individual other impurity is separator, render alkaline with 6 N ammonium hydroxide, and found; and not more than 0.8% of the sum of all other impuriextract with 10 mL of ether: the aqueous layer meets the reties is found (excluding bumetanide related compound A). quirements of the tests for Chloride 〈191〉. Assay— pH 〈791〉: between 4.5 and 6.0, in a solution (1 in 100). Mobile phase, Internal standard solution, Standard preparation, Water, Method I 〈921〉: between 4.0% and 6.0%. and Chromatographic system—Prepare as directed in the Assay under Bumetanide Injection. Residue on ignition 〈281〉: not more than 0.1%. Assay preparation—Weigh and finely powder not fewer than Heavy metals, Method II 〈231〉: not more than 0.001%. 20 Tablets. Transfer an accurately weighed portion of the powLimit of residual solvents— der, equivalent to about 0.5 mg of bumetanide, to a 10-mL Alcohol standard solution—Pipet 2 mL of dehydrated alcohol volumetric flask, add 2.0 mL of Internal standard solution, and into a 100-mL volumetric flask, dilute with water to volume, sonicate for 5 minutes. Add 2.0 mL of water, and mix. Cool, and mix. Transfer 2.0 mL of this solution to a 50-mL volumetric and filter, discarding the first 1 mL of the filtrate. flask, dilute with water to volume, and mix. The resulting soluProcedure—Separately inject equal volumes (about 20 μL) of tion contains 0.08% of alcohol. the Standard preparation and the Assay preparation into the Isopropyl alcohol standard solution—Pipet 2 mL of isopropyl chromatograph, record the chromatograms, and measure the alcohol into a 1000-mL volumetric flask, dilute with water to responses for the major peaks. The relative retention times are volume, and mix. Transfer 2.0 mL of this solution to a 100-mL about 0.7 for 4-ethylbenzaldehyde and 1.0 for bumetanide. volumetric flask, dilute with water to volume, and mix. The reCalculate the quantity, in mg, of bumetanide (C 17H20N2O5S) in sulting solution contains 0.004% of isopropyl alcohol. the portion of Tablets taken by the formula: Test solution—Transfer 1.0 g of Bupivacaine Hydrochloride, accurately weighed, to a 25-mL volumetric flask, dilute with 4C(RU / RS) water to volume, and mix.

of USP Bumetanide Related Compound A RS in methanol, and dilute quantitatively, and stepwise if necessar y, with methanol Packaging and storage-Preserve in well-closed containers.to obtain a solution having a known concentration of about USP Reference standards 〈11〉-0.04mg per mL.
Solution-Dissolve about 230 mg in 15 mL of water in a Procedure-Proceed as directed for Thin-Layer Chromatograseparator, add 1 mL of 6 N ammonium hydroxide, and extract phy under Chromatography 〈621〉.Examine the plate under with three 30-mL portions of chloroform.Evaporate the chloroshort-wavelength UV light.Any secondar y spot obtained from form at room temperature with the aid of a stream of nitrogen, the chromatogram of the Test solution having an RF value correand dry the residue in vacuum.Add 2 mL of chloroform to the sponding to the RF value of the principal spot obtained from residue, and dissolve.the chromatogram of Standard solution 6 is not larger or more intense than the principal spot obtained from the chromato-B: Ultraviolet Absorption 〈197U〉gram of Standard solution 6: not more than 0.2% of bumeta-Solution: 500 µg per mL.nide related compound A is found.For all other secondar y Medium: 0.1 N hydrochloric acid.spots obtained from the chromatogram of the Test solution, Absorptivities at 271 nm, calculated on the anhydrous basis, compare the intensity of each spot with the principal spots obdo not differ by more than 3.0%.tained from the chromatograms of Standard solutions 1 through C: Dissolve about 50 mg in 10 mL of water in a small 5: not more than 0.2% of any individual other impurity is separator, render alkaline with 6 N ammonium hydroxide, and found; and not more than 0.8% of the sum of all other impuriextract with 10 mL of ether: the aqueous layer meets the reties is found (excluding bumetanide related compound A).
Residue on ignition 〈281〉: not more than 0.1%.Assay preparation-Weigh and finely powder not fewer than Heavy metals, Method II 〈231〉: not more than 0.001%.20 Tablets.Transfer an accurately weighed portion of the pow-Limit of residual solventsder, equivalent to about 0.5 mg of bumetanide, to a 10-mL Alcohol standard solution-Pipet 2 mL of dehydrated alcohol volumetric flask, add 2.0 mL of Internal standard solution, and into a 100-mL volumetric flask, dilute with water to volume, sonicate for 5 minutes.Add 2.0 mL of water, and mix.Cool, and mix.Transfer 2.0 mL of this solution to a 50-mL volumetric and filter, discarding the first 1 mL of the filtrate.
flask, dilute with water to volume, and mix.The resulting solu-Procedure-Separately inject equal volumes (about 20 µL) of tion contains 0.08% of alcohol.the Standard preparation and the Assay preparation into the Isopropyl alcohol standard solution-Pipet 2 mL of isopropyl chromatograph, record the chromatograms, and measure the alcohol into a 1000-mL volumetric flask, dilute with water to responses for the major peaks.The relative retention times are volume, and mix.T ransfer 2.0 mL of this solution to a 100-mL about 0.7 for 4-ethylbenzaldehyde and 1.0 for bumetanide.volumetric flask, dilute with water to volume, and mix.The re-Calculate the quantity, in mg, of bumetanide (C 17H20N2O5S) in sulting solution contains 0.004% of isopropyl alcohol.the portion of T ablets taken by the formula: Test solution-Transfer 1.0 g of Bupivacaine Hydrochloride, accurately weighed, to a 25-mL volumetric flask, dilute with 4C(RU / RS) water to volume, and mix. in which C is the concentration, in mg per mL, of USP Bumeta-Chromatographic system-Under typical conditions, the innide RS in the Standard preparation; and RU and RS are the peak strument is equipped with a flame-ionization detector and a 4response ratios obtained from the Assay preparation and the mm × 2-m column that contains packing S3.The carrier gas is Standard preparation, respectively.
nitrogen, flowing at a rate of about 40 mL per minute.The column temperature is maintained at about 175 °, the injection port temperature is maintained at about 200 °, and the detector temperature is maintained at about 280 °.
Procedure-Inject equal volumes (about 5 µL) of the Test solution, the Alcohol standard solution, and the Isopropyl alcohol standard solution successively into the gas chromatograph.Measure the responses of the alcohol peak and the isopropyl USP 35 alcohol peak in each chromatogram.Determine the per centage to contain 0.5% or less of bupivacaine hydrochloride may be of alcohol taken by the formula: packaged in 50-mL multiple-dose containers.
2(rU / rS) USP Reference standards 〈11〉-USP Bupivacaine Hydrochloride RS and determine the per centage of isopropyl alcohol taken by the USP Endotoxin RS formula: Identification-A: Dilute a volume of Injection, equivalent to about 50 mg 0.1(rU / rS) of bupivacaine hydrochloride, with 0.01 N hydrochloric acid to 25 mL, and proceed as directed under Identification-Organic in which rU and rS are the responses of the respective analytes in Nitrogenous Bases 〈181〉, beginning with "T ransfer the liquid to the Test solution and of the corresponding analytes in the Alcoa separator."The Injection meets the requirements of the test.hol standard solution and the Isopropyl alcohol standard solution, B: The retention time of the bupivacaine peak in the chrorespectively.The sum of the content of alcohol and the content matogram of the Assay preparation corresponds to that of the of isopropyl alcohol does not exceed 2%.
bupivacaine peak in the chromatogram of the Standard prepara-Chromatographic puritytion, as obtained in the Assay.Adsorbent: 0.25-mm layer of chromatographic silica gel Bacterial endotoxins 〈85〉-It contains not more than 2.5 mixture.
pH 〈791〉: between 4.0 and 6.5.Mobile phase-Prepare a fresh solution of acetonitrile and pH concentration of 100 µg per mL.
through a membrane filter of 1-µm or finer porosity, and degas.Procedure-Apply separate 10-µL portions of the Test Solu-Internal standard solution-Prepare a solution of dibutyl tion, the Standard solution, and the Diluted standard solution on phthalate in methanol containing about 1.3 mg per mL. the starting line of suitable thin-layer chromatographic plate as Standard preparation-Dissolve about 50 mg of USP Bupivadirected for Thin-Layer Chromatography under Chromatography caine Hydrochloride RS , accurately weighed, in 10.0 mL of 〈621〉.Develop the chromatogram in a suitable chamber until water, using sonication if necessar y, in a 100-mL volumetric the solvent has moved about three-fourths of the length of the flask.Add 10 mL of Internal standard solution, dilute with methplate.Remove the plate from the chamber, mark the solvent anol to volume, and mix.front, and dr y it in warm air.Place the plate in a closed chamber with a dish containing 1 g of iodine in a shallow layer, and Assay preparation-Transfer an accurately measured volume allow to remain for about 5 minutes.Remove the plate from of Injection, equivalent to about 50 mg of bupivacaine hydrothe chamber, spray it with 7 N sulfuric acid, and examine the chloride, to a 100-mL volumetric flask, add 10.0 mL of Internal chromatogram: the RF value of the principal spot from the Test standard solution, dilute with methanol to volume, and mix.solution corresponds to that of the Standard solution, and the Chromatographic system (see Chromatography 〈621〉)-The estimated size and intensity of any other spot obtained from liquid chromatograph is equipped with a 263-nm detector and the Test solution does not exceed that of the principal spot oba 4-mm × 30-cm column that contains packing L1.The flow tained from the Diluted standard solution (0.5%); and the total rate is about 2 mL per minute.Chromatograph three replicate of the estimated sizes and intensities of all of the other spots injections of the Standard preparation, and record the peak reobtained from the Test solution does not exceed four times that sponses as directed for Procedure: the relative standard deviation of the principal spot obtained from the Diluted standard solution of the ratios of the bupivacaine hydrochloride peak to the (2.0%).dibutyl phthalate peak is not more than 1.0%, and the resolu-Assay-Transfer about 600 mg of Bupivacaine Hydrochloride, tion R, factor, between bupivacaine hydrochloride and dibutyl accurately weighed, to a 250-mL conical flask, and dissolve in phthalate is not less than 2.0.20 mL of glacial acetic acid.Add 10 mL of mer curic acetate TS Procedure-Separately inject equal volumes (about 20 µL) of and 3 drops of cr ystal violet TS, and titrate with 0.1 N per chlothe Standard preparation and the Assay preparation into the ric acid VS to a green endpoint.Per form a blank determination, chromatograph, record the chromatograms, and measure the and make any necessar y correction.Each mL of 0.1 N per chloresponses for the major peaks.The relative retention times are ric acid is equivalent to 32.49 mg of C 18H28N2O • HCl. about 1.2 for dibutyl phthalate and 1.0 for bupivacaine hydrochloride.Calculate the quantity, in mg, of C 18H28N2O • HCl in the volume of Injection taken by the formula: .

Bupivacaine Hydrochloride Injection
in which W is the weight, in mg, of USP Bupivacaine Hydro-» Bupivacaine Hydrochloride Injection is a sterile cent of C 18 H 28 N 2 O • HCl, calculated on the anhy-Standard solution 6-Dissolve an accurately weighed quantity drous basis.
Test solution-Dissolve a suitable quantity of Bupivacaine Hy-Other requirements-It meets the requirements under Injecdrochloride in Solvent to obtain a solution containing 20.0 mg Phosphate buffer-Dissolve 1.94 g of monobasic po-Bupivacaine Hydrochloride RS, accurately weighed, in Solvent to tassium phosphate and 2.48 g of dibasic potassium phosphate obtain a solution containing 20.0 mg per mL. in 1000 mL of water.Adjust, if necessar y, with 1 N potassium Diluted standard solution-Quantitatively dilute a portion of hydroxide or 1 M phosphoric acid to a pH of 6.8. the Standard solution in Solvent to obtain a solution having a