Ticarcillin and Clavulanic Acid for Injection »Ticarcillin and Clavulanic Acid for Injection is a sterile,dry mixture of Ticarcillin Disodium and Clavulanate Potassium.It contains the equivalent of not less than 90.0percent and not more than 115.0percent of the labeled amount of ticarcillin (C15H16N2O6S2)and the equivalent of not less than 85.0percent and not more than 120.0percent of the labeled amount of clavulanic acid (C8H9NO5),the labeled amounts representing proportions of ticarcillin to clavulanic acid of 15:1or 30:1. Packaging and storage— Preserve in Containers for Sterile Solidsas described under Injections á1ñ. USP Reference standards á11ñ USP Clavulanate Lithium RS.USP Endotoxin RS.USP Ticarcillin Monosodium Monohydrate RS. Constituted solution— At the time of use,it meets the requirements for Constituted Solutionsunder Injections á1ñ. Identification— The retention times of the major peaks in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation,as obtained in the Assay. Bacterial endotoxins á85ñ It contains not more than 0.07USP Endotoxin Unit per mg of ticarcillin. Sterility á71ñ It meets the requirements when tested as directed for Membrane Filtrationunder Test for Sterility of the Product to be Examined. pHá791ñ: between 5.5and 7.5,in a solution (1in 10). Water,Method Iá921ñ: not more than 4.2%. Particulate matter á788ñ: meets the requirements for small-volume injections. Other requirements— It meets the requirements for Uniformity of Dosage Units á905ñand for Labelingunder Injections á1ñ. Assay— pH4.3sodium phosphate buffer— Dissolve 13.8g of monobasic sodium phosphate in 900mLof water,adjust with phosphoric acid or 10Nsodium hydroxide to a pHof 4.3±0.1,dilute with water to make 1000mL,and mix. Mobile phase— Prepare a suitable mixture of pH4.3sodium phosphate bufferand acetonitrile (95:5),and pass through a membrane filter of 0.5-µm or finer porosity.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ). pH6.4sodium phosphate buffer— Dissolve 6.9g of monobasic sodium phosphate in 900mLof water,adjust with 10Nsodium hydroxide to a pHof 6.4±0.1,dilute with water to make 1000mL,and mix. Clavulanate lithium stock standard solution— Dissolve an accurately weighed quantity of USP Clavulanate Lithium RSin pH6.4sodium phosphate bufferto obtain a solution having a known concentration of about 0.6mg per mL. Standard preparation— Transfer about 100mg of USP Ticarcillin Monosodium Monohydrate RS,accurately weighed,to a 100-mLvolumetric flask,add 150/JmLof Clavulanate lithium stock standard solution,accurately measured,Jbeing the ratio of the labeled amount,in mg,of ticarcillin to the labeled amount,in mg,of clavulanic acid in the Ticarcillin Disodium and Clavulanic Acid for Injection,dilute with pH6.4sodium phosphate bufferto volume,and mix. Assay preparation— Dissolve the contents of 1container of Ticarcillin and Clavulanic Acid for Injection in a volume of water,accurately measured,corresponding to the volume of solvent specified in the labeling.Using a suitable hypodermic needle and syringe,remove all of the withdrawable contents from the container,and dilute quantitatively and stepwise with pH6.4sodium phosphate bufferto obtain a solution having a concentration of about 0.9mg of ticarcillin (C15H16N2O6S2)per mL. Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 220-nm detector and a 4-mm ×30-cm column that contains 3-to 10-µm packing L1.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative retention times are about 0.2for clavulanic acid and 1.0for ticarcillin;the column efficiency determined from the analyte peaks is not less than 1000theoretical plates;the tailing factors for the analyte peaks are not more than 2.0;the resolution,R,between the ticarcillin and clavulanic acid peaks is not less than 5.0;and the relative standard deviation for replicate injections is not more than 2.0%. Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationsinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of ticarcillin (C15H16N2O6S2)in the container of Ticarcillin and Clavulanic Acid for Injection taken by the formula: (L/D)(CP/1000)(rU/rS), in which Lis the labeled quantity,in mg,of ticarcillin in the container;Dis the concentration,in mg per mL,of ticarcillin in the Assay preparationon the basis of the labeled quantity of ticarcillin in the container and the extent of dilution;Cis the concentration,in mg per mL,of USP Ticarcillin Monosodium Monohydrate RSin the Standard preparation;Pis the designated potency,in µg of ticarcillin per mg,of USP Ticarcillin Monosodium Monohydrate RS;and rUand rSare the ticarcillin peak responses obtained from the Assay preparationand the Standard preparation,respectively. Calculate the quantity,in mg,of clavulanic acid (C8H9NO5)in the container of Ticarcillin and Clavulanic Acid for Injection taken by the formula: (L/D)(CP/1000)(rU/rS), in which Lis the labeled quantity,in mg,of clavulanic acid in the container;Dis the concentration,in mg per mL,of clavulanic acid in the Assay preparationon the basis of the labeled quantity of clavulanic acid in the container and the extent of dilution;Cis the concentration,in mg per mL,of USP Clavulanate Lithium RSin the Standard preparation;Pis the designated potency,in µg of clavulanic acid per mg,of USP Clavulanate Lithium RS;and rUand rSare the clavulanic acid peak responses obtained from the Assay preparationand the Standard preparation,respectively. Auxiliary Information— Staff Liaison:William W.Wright,Ph.D.,Scientific Fellow Expert Committee:(PA7)Pharmaceutical Analysis 7 USP28–NF23Page 1928 Phone Number:1-301-816-8335