Cisplatin for Injection
»Cisplatin for Injection is a sterile,lyophilized mixture of Cisplatin,Mannitol,and Sodium Chloride.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of cisplatin (Cl2H6N2Pt).
Caution—Cisplatin is potentially cytotoxic.Great care should be taken in handling the powder and preparing solutions.
Packaging and storage— Preserve in Containers for Sterile Solidsas described under Injections á1ñ.Protect from light.
Constituted solution— At the time of use,it meets the requirements for Constituted Solutionsunder Injections á1ñ.
Identification—
Spray reagent— Prepare as directed for Spray reagentin Identificationtest Cunder Cisplatin.
Standard preparation— Prepare a solution containing 1.0mg of USP Cisplatin RSper mL,9mg of sodium chloride per mL,and 10mg of D-mannitol per mL,in water.
Test preparation— Dissolve the contents of 1container in water to provide a Cisplatin concentration of 1.0mg per mL,based on label claim.
Procedure— Proceed as directed for Procedurein Identificationtest Cunder Cisplatin,beginning with “Apply separately 5-µLquantities.”The principal spot from the Test preparationcorresponds in appearance and RFvalue to that from the Standard preparation.
Bacterial endotoxins á85ñ— It contains not more than 2.0USP Endotoxin Units per mg of cisplatin.
Sterility á71ñ— It meets the requirements when tested as directed for Membrane Filtrationunder Test for Sterility of the Product to be Examined.
Uniformity of dosage units á905ñ: meets the requirements.
pHá791ñ: between 3.5and 6.2,in the solution constituted as directed in the labeling,using Sterile Water for Injection.
Water,Method Iá921ñ— Use anhydrous formamide as the extraction solvent,and use the following procedure.Introduce about 50mLof anhydrous formamide into the titration vessel,and titrate with the Reagentto the electrometric endpoint.Use the formamide thus dried to rinse a suitable glass syringe equipped with a 22-gauge needle,about 8cm long.Add the rinse back to the titration vessel,and again titrate the vessel contents,if necessary.Via the syringe,withdraw 5mLof the formamide thus titrated,and,through the closure of the container,expel the contents into the container.Shake the container to obtain a solution.With the same syringe,withdraw all of the contents of the container,and transfer to the titration vessel.Titrate to the endpoint,adjusting the feeding speed control to the lowest setting,to avoid over-titration.The amount of water found is not more than 2.0%.
Limit of trichloroammineplatinate—
Mobile phase,Standard preparation,and Chromatographic system— Proceed as directed in the test for Limit of trichloroammineplatinateunder Cisplatin.
Test preparation— Using low-actinic volumetric glassware,quantitatively dissolve with water the contents of 1container to yield a 0.5mg per mLsolution of Cisplatin.
Procedure— Proceed as directed for Procedurein the test for Limit of trichloroammineplatinateunder Cisplatin.Calculate the percentage of trichloroammineplatinate taken by the formula:
0.1(318.48/357.58)(rU/rS)(CV/W),
in which 318.48and 357.58are the formula weights of trichloroammineplatinate and potassium trichloroammineplatinate,respectively;rUand rSare the peak areas obtained from the Test preparationand the Standard preparation,respectively;Cis the concentration,in µg per mL,of the Standard preparation;Vis the volume,in mL,of the constituted container contents;and Wis the labeled amount,in mg,of Cisplatin per container.Not more than 1.0%is found.
Limit of transplatin—
Mobile phase,Stock standard solution,Working standard solution,Standard preparation,Resolution solution,and Chromatographic system— Proceed as directed in the test for Limit of transplatinunder Cisplatin.
Test solution— Quantitatively dissolve the contents of 1container with water to yield a 0.5mg per mLsolution of Cisplatin.
Test preparation— Prepare as directed for Test preparationin the test for Transplatinunder Cisplatin.
Procedure— Proceed as directed for Procedurein the test for Limit of transplatinunder Cisplatin.Calculate the percentage of transplatin taken by the formula:
0.1(CV/W)(rU/rS),
in which Cis the concentration,in µg per mL,of the Standard preparation;Vis the volume,in mL,of the constituted container contents;Wis the labeled amount,in mg,of Cisplatin per container;and rUand rSare the peak areas obtained from the Test preparationand the Standard preparation,respectively.Not more than 2.0%is found.
Other requirements— It meets the requirements for Labelingunder Injections á1ñ.
Assay—
Mobile phase,Standard preparation,and Chromatographic system— Proceed as directed in the Assayunder Cisplatin.
Assay preparation— Quantitatively dissolve the Cisplatin in 1container by sonicating for 5minutes with dimethylformamide to yield a Cisplatin concentration of about 1.0mg per mL.Filter 5mLthrough a suitable membrane filter,and collect the filtrate after discarding the first mLpassing through the filter.
Procedure— Proceed as directed for Procedurein the Assayunder Cisplatin.Calculate the quantity,in mg,of Cl2H6N2Pt in the container taken by the formula:
CV(rU/rS),
in which Cis the concentration,in mg per mL,of USP Cisplatin RSin the Standard preparation,Vis the volume,in mL,of the constituted container contents,and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(PA6)Pharmaceutical Analysis 6
USP28–NF23Page 482
Phone Number:1-301-816-8389