Diluted phosphoric acid,Solvent,Mobile phase,andChromatographic system— Proceed as directed in the test for Chromatographic purityunder Meropenem.

Standard solution— Prepare a solution of USP Meropenem RSin Solventhaving a known concentration of about 0.029mg of USP Meropenem RSper mL.[NOTE—Immediately after preparation,store this solution in a refrigerator.It may be used for 24hours.]

Test solution— Transfer an accurately measured volume of Injection,equivalent to about 50mg of meropenem,based on the labeled amount,to a 10-mLvolumetric flask,dilute with Solventto volume,and mix.Use this Test solutionimmediately.

Procedure— Proceed as directed in the test for Chromatographic purityunder Meropenem.Calculate the percentage of each impuity in the portion of Injection taken by the formula: in which Cis the concentration,in mg per mL,of USP Meropenem RSin the Standard solution;Pis the stated percentage,calculated on the anhydrous basis,of meropenem in USP Meropenem RS;mis the amount,in mg,of meropenem in the portion of Injection taken to prepare the Test solution,based on the label claim;riis the peak response of any individual impurity obtained from the Test solution;and rSis the peak response of meropenem obtained from the Standard solution.Not more than 0.8%of the impurity,if any,with a retention time of about 0.45relative to that of meropenem,is found;and not more than 0.6%of the impurity,if any,with a retention time of about 1.9relative to that of meropenem,is found.

Potassium chloride solution— Transfer 38.1g of potassium chloride to a 1000-mLvolumetric flask,dissolve in and dilute with water to volume,and mix.

Standard sodium solution— Dissolve 25.42mg of sodium chloride,previously dried at 105for 2hours and accurately weighed,quantitatively in water to obtain a solution having a concentration of 25.42µg of sodium chloride per mL.Transfer 5.0mLof this solution to a 50-mLvolumetric flask,add 5.0mLof Potassium chloride solution,dilute with water to volume,and mix.

Test solution— Transfer an accurately measured volume of the stock solution used to prepare Assay preparation 1or Assay preparation 2,as appropriate,equivalent to about 25mg of meropenem,to a 200-mLvolumetric flask,dilute with water to volume,and mix.Transfer 5.0mLof this solution to a 50-mLvolumetric flask,add 5.0mLof Potassium chloride solution,dilute with water to volume,and mix.

Blank solution— Transfer 5.0mLof Potassium chloride solutionto a 50-mLvolumetric flask,dilute with water to volume,and mix.

Procedure— Concomitantly determine the absorbances of the Standard sodium solutionand the Test solutionat the sodium emission line at 589.6nm with an atomic absorption spectrophotometer (see Spectrophotometry and Light-Scattering á851ñ),equipped with a sodium hollow-cathode lamp and a single-slot burner,using an air–acetylene flame and the Blank solutionas the blank.Calculate the quantity,in mg,of sodium (Na)in the constituted Meropenem for Injection by the formula: in which 22.99and 58.44are the atomic weight of sodium and the molecular weight of sodium chloride,respectively;Cis the concentration,in µg per mL,of sodium chloride in the Standard sodium solution;Vis the volume,in mL,of the stock solution obtained in Assay preparation 1or Assay preparation 2,as appropriate;vis the volume,in mL,of the portion of the stock solution taken to prepare the Test solution;Mis the total quantity,in mg,of meropenem in the stock solution obtained in Assay preparation 1or Assay preparation 2,as appropriate,based on the result of the Assay;and AUand ASare the absorbances of theTest solutionand the Standard sodium solution,respectively:it contains between 80%and 120%of the labeled amount of sodium.

Mobile phase— Dilute 15mLof tetrabutylammonium hydroxide solution (25%in water)with water to 750mL.Adjust with dilute phosphoric acid (1in 10)to a pHof 7.5±0.1.Add 150mLof acetonitrile and 100mLof methanol,mix,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard preparation— Dissolve an accurately weighed portion of USP Meropenem RSquantitatively in Mobile phaseto obtain a solution having a known concentration of about 0.11mg per mL.This solution contains the equivalent of about 0.1mg of meropenem per mL.[NOTE—Immediately after preparation,store this solution in a refrigerator and use within 24hours.]

Assay preparation 1(where it is represented as being a single-dose container)— Constitute a container of Meropenem for Injection with a volume of water,accurately measured,corresponding to the amount of solvent specified in the labeling.Withdraw all of the withdrawable contents,using a suitable hypodermic needle and syringe,and transfer to a 100-mLvolumetric flask.Dilute with water to volume,and mix.Dilute an accurately measured volume of this stock solution quantitatively with Mobile phaseto obtain a solution having a concentration of about 0.1mg of meropenem per mL.Hold this Assay preparation 1for 2hours at 25±1before testing.

Assay preparation 2(where the label states the quantity of meropenem in a given volume of constituted solution)— Constitute a container of Meropenem for Injection with a volume of water,accurately measured,corresponding to the amount of solvent specified in the labeling.Transfer an accurately measured volume of the constituted solution,equivalent to about 100mg of meropenem to a 100-mLvolumetric flask.Transfer 5.0mLof this stock solution to a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.Hold this Assay preparation 2for 2hours at 25±1before testing.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 300-nm detector and a 4.6-mm ×25-cm column that contains 5-µm packing L1.The flow rate is about 1.5mLper minute.Adjust the flow rate to obtain a retention time for meropenem of about 6to 8minutes.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency is not less than 2500theoretical plates;the tailing factor is not more than 1.5;and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 20µL)of Standard preparation,Assay preparation 1,and Assay preparation 2into the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the quantity,in mg,of meropenem (C17H25N3O5S)withdrawn from the container or in the portion of constituted solution taken by the formula: in which Lis the labeled quantity,in mg,of meropenem in the container or in the volume of constituted solution taken;Dis the concentration,in mg per mL,of meropenem in Assay preparation 1or Assay preparation 2,based on the labeled quantity in the container or in the portion of constituted solution taken,respectively;Cis the concentration,in mg per mL,of USP Meropenem RSin the Standard preparation,calculated on the anhydrous basis;Pis the stated percentage,on the anhydrous basis,of meropenem in USP Meropenem RS;and rUand rSare the peak responses of meropenem obtained from Assay preparation 1or Assay preparation 2,as appropriate,and the Standard preparation,respectively.