Ampicillin for Injectable Suspension
»Ampicillin for Injectable Suspension is a dry mixture of ampicillin trihydrate and one or more suitable buffers,preservatives,stabilizers,and suspending agents.It contains the equivalent of not less than 90.0percent and not more than 120.0percent of the labeled amount of ampicillin (C16H19N3O4S).
Packaging and storage— Preserve in Containers for Sterile Solidsas described under Injections á1ñ.
Identification— Dissolve a quantity in a mixture of acetone and 0.1Nhydrochloric acid (4:1)to obtain a solution containing 5mg of ampicillin per mL:the resulting solution responds to the Identificationtest under Ampicillin Capsules.
Bacterial endotoxins á85ñ— It contains not more than 0.15Endotoxin Unit per mg of ampicillin.
pHá791ñ: between 5.0and 7.0,in the suspension constituted as directed in the labeling.
Water,Method Iá921ñ: between 11.4%and 14.0%.
Sterility á71ñ— It meets the requirements when tested as directed for Antibiotic Solids,Bulks,and Blendsin the section Membrane Filtrationunder Test for Sterility of the Product to be Examined,except to use Fluid D,to which has been added sufficient sterile penicillinase to inactivate the ampicillin and to swirl the vessel until solution is complete before filtering.If it does not dissolve completely,proceed as directed for Solidsin the section Direct Inoculation of the Culture Mediumunder Test for Sterility of the Product to be Examined,except to use Fluid Thioglycollate Medium and Soybean–Casein Digest Medium containing sufficient penicillinase to inactivate the ampicillin in each vessel.
Other requirements— It meets the requirements for Uniformity of Dosage Units á905ñ,and for Labelingunder Injections á1ñ.
Assay—
Phosphate buffer solution— Accurately weigh 68g of monobasic potassium phosphate,and transfer to a 500-mLvolumetric flask.Dissolve in and dilute with water to volume.
Mobile phase— Prepare a suitable mixture of water,acetonitrile,Phosphate buffer solution,and glacial acetic acid (3600:360:40:4).Pass through a 0.45-µm nylon filter,and degas.
Standard preparation— Dissolve,with sonication,an accurately weighed quantity of USP Ampicillin RSin water to prepare a solution having 0.5mg per mL.Pass through a 0.45-µm PTFEfilter,discarding the first 3mLof the filtrate.
Caffeine solution— Transfer about 30mg of caffeine,accurately weighed,to a 50-mLvolumetric flask.Add 25mLof water,sonicate to dissolve,and dilute with water to volume.Pass through a 0.45-µm PTFEfilter,discarding the first 3mLof the filtrate.
System suitability solution— Prepare a solution of 1.0mLofCaffeine solutionand 9.0mLofStandard preparation,and mix.
Assay preparation— Quantitatively dilute an accurately measured volume of Ampicillin for Injectable Suspension,constituted as directed in the labeling,with water to obtain a solution containing about 0.5mg per mL.Pass through a 0.45-µm PTFEfilter,discarding the first 3mLof the filtrate.
Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×30-cm analytical column that contains 10-µm packing L1.The flow rate is about 2.0mLper minute.The column temperature is maintained at 40.Chromatograph theSystem suitability solutionand theStandard preparation,and record the peak responses as directed forProcedure:the order of elution is ampicillin followed by caffeine;the resolution,R,between ampicillin and caffeine is greater than 2;the column efficiency is not less than 2000theoretical plates for the ampicillin peak;the tailing factor is not greater than 1.4;and the relative standard deviation for replicate injections of theStandard preparationis not more than 2.0%.
Procedure— Separately inject equal volumes (about 20µL)of theStandard preparationand theAssay preparationinto the chromatograph,record the chromatograms,and measure the areas of the major peaks.Calculate the quantity,in mg,of ampicillin (C16H19N3O4S)in each mLof the constituted solution of Ampicillin for Injectable Suspension taken by the formula:
CD(rU/rS),
in whichCis the concentration,in mg per mL,of USP Ampicillin RSin theStandard preparation;Dis the dilution factor used in preparing the Assay preparation;andrUandrSare the average peak responses of the ampicillin peaks obtained from theAssay preparationand theStandard preparation,respectively.
Auxiliary Information— Staff Liaison:Ian DeVeau,Ph.D.,Senior Scientist
Expert Committee:(VET)Veterinary Drugs
USP28–NF23Page 153
Pharmacopeial Forum:Volume No.28(6)Page 1766
Phone Number:1-301-816-8178