A: Infrared Absorption á197Kñ.

B: The retention time of the loracarbef peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.

Solution A— Dissolve 6.9g of monobasic ammonium phosphate in 1960mLof water.Adjust with phosphoric acid to a pHof 2.5,add 40mLof acetonitrile,and mix.Filter,if necessary,to obtain a clear solution,and degas.

Solution B— Dissolve 6.9g of monobasic ammonium phosphate in 600mLof water.Adjust with phosphoric acid to a pHof 2.5,add 1400mLof acetonitrile,and mix.Filter,if necessary,to obtain a clear solution,and degas.

Mobile phase— Use variable mixtures of Solution Aand Solution Bas directed for Chromatographic system.

NOTE—When preparing the System suitability solution,the Standard solution,and the Test solution,if necessary,sonicate and mix on a vortex mixer to aid in dissolution.Use the solutions immediately after preparation or refrigerate and use within 24hours.

Phenylglycine solution— Dissolve an accurately weighed quantity of phenylglycine in Solution Ato obtain a solution having a known concentration of about 0.0075mg per mL.

System suitability solution— Dissolve accurately weighed quantities of USP Loracarbef RSand USP Cefaclor RSin Solution Ato obtain a solution having known concentrations of about 0.01mg of each per mL.

Standard solution— Dissolve an accurately weighed quantity of USP Loracarbef RSin Solution Ato obtain a solution having a known concentration of about 0.01mg per mL.

Test solution— Transfer about 50mg of Loracarbef,accurately weighed,to a 10-mLvolumetric flask,add about 8mLof Solution A,and dissolve.Dilute with Solution Ato volume,and mix.Filter,if necessary,to obtain a clear solution.

Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm ×15-cm column that contains 5-µm packing L1.The flow rate is about 2mLper minute,and is maintained at a constant temperature of about 40.The chromatograph is programmed as follows.Initially it is equilibrated with Solution A,then the proportion of Solution Bis increased linearly from 0%to 14.5%over 9.5minutes,then increased from 14.5%to 100%over 7.5minutes,and held at 100%for an additional 1.5minutes.Finally,the composition of the Mobile phaseis changed to 100%Solution A,and is allowed to re-equilibrate for about 4minutes or until a stable baseline is obtained.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.9for cefaclor and 1.0for loracarbef;the resolution,R,between the cefaclor peak and the loracarbef peak is between 4.0and 8.0;and the tailing factor for the loracarbef peak is not more than 1.3.Calculate the recovery of loracarbef from the System suitability solutionby the formula: in which Cis the concentration,in mg per mL,of USP Loracarbef RSin the Standard solution;Lis the concentration,in mg per mL,of USP Loracarbef RSin the System suitability solution;and rLand rSare the loracarbef responses in the chromatograms obtained from the System suitability solutionand the Standard solution,respectively:the recovery is between 95%and 105%.

Procedure— Separately inject equal volumes (about 20µL)of Solution A,the Phenylglycine solution,the Standard solution,and the Test solutioninto the chromatograph,record the chromatograms,and measure the peak responses.Disregard any peak responses in the chromatograms that correspond to those in the chromatogram obtained from Solution A,and identify any peak in the chromatogram of the Test solutionthat corresponds to the peak for phenylglycine in the chromatogram obtained from the Phenylglycine solution.Separately calculate the percentage of each related compound in the portion of Loracarbef taken by the formula: in which Yis the concentration,in mg per mL,of Loracarbef in the Test solution;rYis the response of any related compound in the chromatogram obtained from the Test solution;and Cand rSare as defined above:not more than 0.15%of phenylglycine is found,not more than 0.5%of any other related compound is found,and the sum of all other related compounds is not more than 2.0%.

Mobile phase— Dissolve 2.0g of sodium 1-pentanesulfonate in 1560mLof water,add 20mLof triethylamine,and adjust with phosphoric acid to a pHof 2.5.Add 440mLof methanol,mix,and pass through a filter having a porosity of 0.5µm or finer,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Standard preparation— Transfer about 10mg of USP Loracarbef RS,accurately weighed,to a 50-mLvolumetric flask,dissolve in Mobile phase,using sonication,if necessary,to achieve dissolution,dilute with Mobile phaseto volume,and mix.

Assay preparation— Transfer about 10mg of Loracarbef,accurately weighed,to a 50-mLvolumetric flask,dissolve in Mobile phase,using sonication,if necessary,to achieve dissolution,dilute with Mobile phaseto volume,and mix.

Resolution solution— Prepare a solution in Mobile phasecontaining about 0.2mg each of USP Loracarbef RSand of USP Loracarbef L-Isomer RSin each mL.

Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 265-nm detector and a 4.6-mm ×25-cm column that contains 5-µm packing L1.The flow rate is about 1.5mLper minute.Chromatograph the Resolution solution,and record the responses as directed for Procedure:the relative retention times are about 0.6for loracarbef L-isomer and 1.0for loracarbef;and the resolution,R,between the loracarbef L-isomer peak and the loracarbef peak is not less than 6.0.Chromatograph the Standard preparation,and record the responses as directed for Procedure:the capacity factor for the loracarbef peak is not less than 5and not more than 8;the tailing factor is not less than 0.8and not more than 1.3;the column efficiency,determined from the loracarbef peak,is not less than 2500theoretical plates;and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— [NOTE—Use peak areas where peak responses are indicated.]Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in µg,of anhydrous loracarbef (C16H16ClN3O4)in each mg of the Loracarbef taken by the formula: in which Wis the quantity,in mg,of USP Loracarbef RStaken to prepare the Standard preparation;Pis the assigned potency,in µg of anhydrous loracarbef (C16H16ClN3O4)in each mg of USP Loracarbef RS;wis the quantity,in mg,of Loracarbef taken to prepare the Assay preparation;and rUand rSare the loracarbef peak responses obtained from the Assay preparationand the Standard preparation,respectively.