Ticarcillin Monosodium
C15H15N2NaO6S2·H2O 424.43

4-Thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid,6-[(carboxy-3-thienylacetyl)amino]-3,3-dimethyl-7-oxo,monosodium salt,[2S-2a,5a,6b(S*)]-,monohydrate.

(R)-N-[(2S,5R,6R)-2-Carboxy-3,4-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-6-yl-]3-thiophenemalonamic acid monosodium salt.

Anhydrous 406.42 [74682-62-5].
»Ticarcillin Monosodium contains the equivalent of not less than 890µg of ticarcillin (C15H16N2O6S2)per mg,calculated on the anhydrous basis.
Packaging and storage— Preserve in tight containers.
Labeling— Where it is intended for use in preparing injectable dosage forms,the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms.
Identification—
A: Infrared Absorption á197Kñ.
B: Ultraviolet Absorption á197Uñ—
Solution: 20µg per mL,obtained as follows.Transfer about 40mg,accurately weighed,to a 100-mLvolumetric flask,dissolve in and dilute with water to volume,and mix.Transfer 5.0mLof this solution to a second 100-mLvolumetric flask,dilute with 0.1Nmethanolic hydrochloric acid (0.8mLof hydrochloric acid diluted with methanol to 100mL)to volume,and mix.Record the spectrum between 200and 300nm.
C: Asolution (1in 20)responds to the tests for Sodium á191ñ.
Specific rotation á781Sñ: between +181and +197.
Test solution: 10mg per mL,in pH6.4sodium phosphate buffer,prepared as directed in the Assay.
Crystallinity á695ñ: meets the requirements.
pHá791ñ: between 2.5and 4.0,in a solution containing the equivalent of 10mg of ticarcillin per mL.
Water,Method Iá921ñ: between 4.0%and 6.0%.
Dimethylaniline á223ñ: meets the requirement.
Other requirements— Where the label states that Ticarcillin Monosodium is sterile,it meets the requirements for Sterility á71ñand for Bacterial endotoxinsunder Ticarcillin for Injection.Where the label states that Ticarcillin Monosodium must be subjected to further processing during the preparation of injectable dosage forms,it meets the requirements for Bacterial endotoxinsunder Ticarcillin for Injection.
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.
Standard preparation— Transfer about 50mg of USP Ticarcillin Monosodium Monohydrate RS,accurately weighed,to a 50-mLvolumetric flask,dilute with pH6.4sodium phosphate bufferto volume,and mix.
Resolution solution— Transfer about 25mg of USP Ticarcillin Monosodium Monohydrate RS,accurately weighed,to a 25-mLvolumetric flask.Prepare a solution of USP Clavulanate Lithium RSin pH6.4sodium phosphate buffercontaining the equivalent of about 0.15mg of clavulanic acid per mL.Place 5mLof this solution in the 25-mLvolumetric flask,dilute with pH6.4sodium phosphate bufferto volume,and mix.[NOTE—Use this solution on the day prepared.]
Assay preparation— Transfer about 50mg of Ticarcillin Monosodium,accurately weighed,to a 50-mLvolumetric flask,dilute with pH6.4sodium phosphate bufferto volume,and mix.
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 Resolution solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.2for clavulanic acid and 1.0for ticarcillin;and the resolution,R,between the clavulanic acid peak and the ticarcillin peak is not less than 5.0.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency is not less than 1000theoretical plates;the tailing factor is not more than 2.0;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 preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in µg,of ticarcillin (C15H16N2O6S2)in each mg of the Ticarcillin Monosodium taken by the formula:
50(CP/W)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Ticarcillin Monosodium Monohydrate RSin the Standard preparation;Pis the designated potency,in µg of ticarcillin (C15H16N2O6S2)per mg,of USP Ticarcillin Monosodium Monohydrate RS;Wis the weight,in mg,of Ticarcillin Monosodium taken to prepare the Assay preparation;and rUand rSare the ticarcillin 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 1929
Phone Number:1-301-816-8335