Diluted phosphoric acid, Solvent, Mobile phase, and Chromatographic system— Proceed as directed in the test for Chromatographic purity under Meropenem.

Standard solution— Prepare a solution of USP Meropenem RS in Solvent having a known concentration of about 0.029 mg of USP Meropenem RS per mL. [note—Immediately after preparation, store this solution in a refrigerator. It may be used for 24 hours.]

Test solution— Transfer an accurately weighed portion of Meropenem for Injection, equivalent to about 50 mg of meropenem, based on the labeled amount, to a 10-mL volumetric flask, dilute with Solvent to volume, and mix. Use this Test solution immediately.

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

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

Standard sodium solution— Dissolve 25.42 mg of sodium chloride, previously dried at 105 for 2 hours and accurately weighed, quantitatively in water to obtain a solution having a concentration of 25.42 µg of sodium chloride per mL. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, add 5.0 mL of 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 1 or Assay preparation 2, as appropriate, equivalent to about 25 mg of meropenem, to a 200-mL volumetric flask, dilute with water to volume, and mix. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, add 5.0 mL of Potassium chloride solution, dilute with water to volume, and mix.

Blank solution— Transfer 5.0 mL of Potassium chloride solution to a 50-mL volumetric flask, dilute with water to volume, and mix.

Procedure— Concomitantly determine the absorbances of the Standard sodium solution and the Test solution at the sodium emission line at 589.6 nm with an atomic absorption spectrophotometer (see Spectrophotometry and Light-Scattering 851), equipped with a sodium hollow-cathode lamp and a single-slot burner, using an air–acetylene flame and the Blank solution as the blank. Calculate the quantity, in mg, of sodium (Na) in the constituted Meropenem for Injection by the formula: in which 22.99 and 58.44 are the atomic weight of sodium and the molecular weight of sodium chloride, respectively; C is the concentration, in µg per mL, of sodium chloride in the Standard sodium solution; V is the volume, in mL, of the stock solution obtained in Assay preparation 1 or Assay preparation 2, as appropriate; v is the volume, in mL, of the portion of the stock solution taken to prepare the Test solution; M is the total quantity, in mg, of meropenem in the stock solution obtained in Assay preparation 1 or Assay preparation 2, as appropriate, based on the result of the Assay; and AU and AS are the absorbances of the Test solution and the Standard sodium solution, respectively: it contains between 80% and 120% of the labeled amount of sodium.

Change to read:

Mobile phase— Dilute 15 mL of tetrabutylammonium hydroxide solution (25% in water) with water to 750 mL. Adjust with dilute phosphoric acid (1 in 10) to a pH of 7.5 ± 0.1. Add 150 mL of acetonitrile and 100 mL of methanol, mix, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).

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

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-mL volumetric flask. Dilute with water to volume, and mix. Dilute an accurately measured volume of this stock solution quantitatively with Mobile phase to obtain a solution having a concentration of about 0.1 mg of meropenem per mL. Hold this Assay preparation 1 for 2 hours at 25 ± 1 before 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 100 mg of meropenem to a 100-mL volumetric flask, and dilute with water to volume.USP31 Transfer 5.0 mL of this stock solution to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix. Hold this Assay preparation 2 for 2 hours at 25 ± 1 before testing.

Chromatographic system (see Chromatography 621)— 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 1.5 mL per minute. Adjust the flow rate to obtain a retention time for meropenem of about 6 to 8 minutes. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 2500 theoretical 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 20 µL) of Standard preparation, Assay preparation 1, and Assay preparation 2 into 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 L is the labeled quantity, in mg, of meropenem in the container or in the volume of constituted solution taken; D is the concentration, in mg per mL, of meropenem in Assay preparation 1 or Assay preparation 2, based on the labeled quantity in the container or in the portion of constituted solution taken, respectively; C is the concentration, in mg per mL, of USP Meropenem RS in the Standard preparation, calculated on the anhydrous basis; P is the stated percentage, on the anhydrous basis, of meropenem in USP Meropenem RS; and rU and rS are the peak responses of meropenem obtained from Assay preparation 1 or Assay preparation 2, as appropriate, and the Standard preparation, respectively.