A: Infrared Absorption 197M.

B: Ultraviolet Absorption 197U—

C: Dissolve 1 mg of it in 4 mL of water, add 1 mL of 1 N sulfuric acid while cooling in an ice bath, add 1 mL of a freshly prepared solution of sodium nitrite (1 in 100), allow to stand for 2 minutes, then add 1 mL of ammonium sulfamate solution (1 in 100). Allow to stand for 1 minute, and add 1 mL of N-(1-naphthyl)ethylenediamine dihydrochloride TS: a red-purple color develops.

Test solution: 10 mg per mL, in methanol.

Solution A— Prepare filtered and degassed 0.02 M ammonium acetate.

Solution B— Use filtered and degassed acetonitrile.

Mobile phase— Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).

Diluent— Prepare a degassed mixture of water and acetonitrile (2:1).

System suitability solution— Dissolve a quantity of USP Cefpodoxime Proxetil RS in Diluent to obtain a solution containing about 10 µg per mL. [NOTE—A volume of methanol not exceeding 10% of the total volume in the final solution may be used to facilitate dissolution.]

Test solution— Transfer about 50 mg of Cefpodoxime Proxetil, accurately weighed, to a 50-mL volumetric flask, dissolve in 5 mL of methanol, using sonication if necessary, dilute with Diluent to volume, and mix. This solution should be injected promptly, but may be analyzed within 24 hours when stored at 8.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 260-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The column temperature is maintained at a constant temperature of about 30. The flow rate is about 2 mL per minute. The chromatograph is programmed as follows. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the retention time for cefpodoxime proxetil R-epimer is between 37 and 42 minutes; the relative retention times are about 0.9 for cefpodoxime proxetil S-epimer and 1.0 for cefpodoxime proxetil R-epimer; the resolution, R, between cefpodoxime proxetil S-epimer and cefpodoxime proxetil R-epimer is not less than 4.0; the column efficiency is not less than 19,000 theoretical plates determined from the cefpodoxime proxetil R-epimer peak; and the relative standard deviation for replicate injections determined from the sum of the areas of the cefpodoxime proxetil S-epimer and cefpodoxime proxetil R-epimer peaks is not more than 2.0%.

Procedure— Inject a volume (about 20 µL) of the Test solution into the chromatograph, record the chromatogram, and measure all of the peak areas. Calculate the percentage of each impurity in the portion of Cefpodoxime Proxetil taken by the formula: in which ri is the peak area for each impurity; and rs is the sum of the areas of all the peaks: not more than 3.0% of any peak at a relative retention time of about 0.86 is found; not more than 1.0% for any peak at relative retention times of about 1.27, 1.39, and other individual peaks having relative retention times higher than 2.0 is found; not more than 0.5% of any other individual impurity is found; and not more than 6.0% of total impurities is found, impurity peaks of less than 0.05% being disregarded.

(Official January 1, 2007)

Mobile phase— Prepare a filtered and degassed mixture of 0.02 M ammonium acetate and acetonitrile (6:4). Make adjustments if necessary (see System Suitability under Chromatography 621).

Diluent— Prepare a degassed mixture of water and acetonitrile (6:4).

Standard preparation— Transfer about 25 mg of USP Cefpodoxime Proxetil RS, accurately weighed, to a 50-mL volumetric flask, dissolve in 5 mL of methanol, dilute with Diluent to volume, and mix. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, dilute with Diluent to volume, mix, and pass through a filter having a 0.45-µm or finer porosity.

Assay preparation— Transfer about 50 mg of Cefpodoxime Proxetil, accurately weighed, to a 100-mL volumetric flask, dissolve in 10 mL of methanol, dilute with Diluent to volume, and mix. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, dilute with Diluent to volume, mix, and pass through a filter having a 0.45-µm or finer porosity

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 235-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 2 mL per minute. The column temperature is maintained at a constant temperature of about 30. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.9 for cefpodoxime proxetil S-epimer and 1.0 for cefpodoxime proxetil R-epimer; the resolution, R, between cefpodoxime proxetil S-epimer and cefpodoxime proxetil R-epimer is not less than 2.5; the tailing factor for cefpodoxime proxetil R-epimer is not more than 1.5; and the relative standard deviation determined from the sum of the areas of the cefpodoxime proxetil S-epimer and cefpodoxime proxetil R-epimer peaks for replicate injections is not more than 1.0%.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity in µg of cefpodoxime (C15H17N5O6S2) in each mg of Cefpodoxime Proxetil taken by the formula: in which C is the concentration, in mg per mL, of USP Cefpodoxime Proxetil RS in the Standard preparation; P is the designated potency, in µg per mg, of cefpodoxime (C15H17N5O6S2) in USP Cefpodoxime Proxetil RS; W is the weight, in mg, of Cefpodoxime Proxetil taken to prepare the Assay preparation; and rU and rS are the sums of the peak responses for cefpodoxime proxetil S-epimer and cefpodoxime proxetil R-epimer obtained from the Assay preparation and the Standard preparation, respectively.