A: Infrared Absorption á197Kñ.

B: Ultraviolet Absorption á197Uñ—

Test solution: 5mg per mL,in water.

Sodium sulfide reagent— Dissolve 5g of sodium sulfide in a mixture of 10mLof water and 30mLof glycerin.Preserve in well-filled,light-resistant bottles,and use within 3months.

Test solution— Transfer 1.0g of Meropenem to a quartz or porcelain crucible,cover loosely with a lid,and carbonize by gentle ignition.After cooling,add 2mLof nitric acid and 5drops of sulfuric acid,heat cautiously until white fumes evolve,and incinerate by ignition at 500to 600.Cool,add 2mLof hydrochloric acid,and evaporate on a water bath to dryness.Moisten the residue with 3drops of hydrochloric acid,add 10mLof hot water,and warm for 2minutes.Add 1drop of phenolphthalein TS,add ammonia TS,dropwise,until the solution develops a pale red color,and add 2mLof 1Nacetic acid.Filter,if necessary,to obtain a clear solution,washing the filter with 10mLof water.Transfer the filtrate and the washing to a 50-mLcolor-comparison tube,and add water to obtain a volume of 50mL.

Standard solution— Evaporate a mixture of 2mLof nitric acid,5drops of sulfuric acid,and 2mLof hydrochloric acid on a water bath,further evaporate to dryness on a hot sand bath,and moisten the residue with 3drops of hydrochloric acid.Proceed as directed for Test solution,beginning with “add 10mLof hot water,”except add water to obtain a volume of 49mL.Add 1.0mLof Standard Lead Solution(see Heavy Metals á231ñ).

Procedure— To the tubes containing the Test solutionand the Standard solution,add 1drop of Sodium sulfide reagent,mix,and allow to stand for 5minutes.The color in the tube containing the Test solutionis not darker than the color in the tube containing the Standard solution(0.001%).

Internal standard solution— Prepare a solution in dimethylformamide containing 0.05µLof ethyl acetate per mL.

Standard solution— Transfer about 50mg of acetone,accurately weighed,to a 100-mLvolumetric flask,dilute with dimethylformamide to volume,and mix.To 1.0mLof this solution,add 10.0mLof the Internal standard solution,and mix.

Test solution— Dissolve 100mg of Meropenem,accurately weighed,in 0.2mLof dimethylformamide and 2.0mLof Internal standard solution.

Chromatographic system (see Chromatography á621ñ)— The gas chromatograph is equipped with a flame-ionization detector and a 3-mm ×2-m column that contains support S2and is maintained at a constant temperature of about 150.The injection port temperature is maintained at about 170.Nitrogen is the carrier gas,with the flow rate adjusted so that the retention time for acetone is about 3minutes.

Procedure— Separately inject equal volumes (about 2µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the peak responses for the acetone peak and the internal standard peak.Calculate the percentage of acetone in the portion of Meropenem taken by the formula: in which WAis the weight,in mg,of acetone in the Standard solution;WUis the quantity,in mg,of Meropenem in the Test solution;and RUand RSare the peak area ratios of acetone to the internal standard obtained from the Test Solutionand the Standard solution,respectively.Not more than 0.05%is found.

Diluted phosphoric acid— Dilute 10mLof phosphoric acid with water to make 100mLof solution.

Solvent— Transfer 1.0mLof triethylamine to a 1000-mLvolumetric flask containing 900mLof water.Adjust with Diluted phosphoric acidto a pHof 5.0±0.1,dilute with water to volume,and mix.

Mobile phase— Transfer 1.0mLof triethylamine to a 1000-mLvolumetric flask containing 900mLof water.Adjust with Diluted phosphoric acidto a pHof 5.0±0.1,dilute with water to volume,and mix.Mix this solution with 70mLof acetonitrile.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard solution— Prepare a solution of USP Meropenem RSin Solventhaving a known concentration of about 0.025mg of USP Meropenem RSper mL.[NOTE—Immediately after preparation,store this solution in a refrigerator and use within 24hours.]

Test solution— Dissolve an accurately weighed quantity of Meropenem quantitatively in Solventto obtain a solution having a known concentration of about 5mg per mL.Use this Test solutionimmediately.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm ×25-cm column that contains 5-µm packing L1and is maintained at a constant temperature of about 40.The flow rate is about 1.6mLper minute,and is adjusted so that the retention time of meropenem is between 5and 7minutes.Chromatograph the Standard solution,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 10µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,using a period of chromatography for the Test solutionthat is about 3times the retention time of meropenem,and measure the peak responses.Major impurity peaks may be observed at retention times of about 0.45and 1.9in relation to the retention time of meropenem.Calculate the percentage of each impurity in the chromatogram obtained from the Test solutionby the formula: in which CSis the concentration,in mg per mL,of USP Meropenem RSin the Standard solution;CUis the concentration,in mg per mL,of Meropenem in the Test solution;Pis the stated percentage,calculated on the anhydrous basis,of meropenem in USP Meropenem RS;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 0.3%of any of two major impurities is found,calculated on the dried basis;not more than 0.1%of any other impurity is found,calculated on the dried basis;and the sum of all such other impurities is not more 0.3%.

Diluted phosphoric acid— Dilute 10mLof phosphoric acid with water to make 100mLof solution.

Solvent— Transfer 1.0mLof triethylamine to a 1000-mLvolumetric flask containing 900mLof water.Adjust with Diluted phosphoric acidto a pHof 5.0±0.1,dilute with water to volume,and mix.

Mobile phase— Prepare a mixture of Solventand methanol (5:1).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard preparation— Transfer about 25mg of USP Meropenem RS,accurately weighed,to a 50-mLvolumetric flask,add Solvent,swirl to dissolve,dilute with Solventto volume,and mix.[NOTE—Immediately after preparation,store this solution in a refrigerator.It may be used for 24hours.]

Assay preparation— Transfer about 25mg of Meropenem,accurately weighed,to a 50-mLvolumetric flask,add Solvent,swirl to dissolve,dilute with Solventto volume,and mix.Use this solution immediately after preparation.

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.Adjust the flow rate so that the retention time for meropenem is about 6to 8minutes.The flow rate is about 1.5mLper minute.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 5µL)of Standard preparationand Assay preparationinto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the quantity,in mg,of C17H25N3O5Sin the portion of Meropenem taken by the formula: in which WSis the weight,in mg,of USP Meropenem RStaken to prepare the Standard preparation,calculated on the anhydrous basis;WUis the weight,in mg,of Meropenem taken to prepare the Assay preparation;Pis the stated percentage,calculated on the anhydrous basis,of meropenem in USP Meropenem RS;and rUand rSare the meropenem peak responses obtained from the Assay preparationand the Standard preparation,respectively.