Ifosfamide for Injection
»Ifosfamide for Injection contains not less than 90.0percent and not more than 110.0percent of the labeled amount of C7H15Cl2N2O2P.
Caution—Great care should be taken in handling Ifosfamide,as it is a potent cytotoxic agent and suspected carcinogen.
Packaging and storage— Preserve in Containers for Sterile Solidsas described under Injections á1ñ,at controlled room temperature.
Constituted solution— At the time of use,it meets the requirements for Constituted Solutionsunder Injections á1ñ.
Identification—
A: (See Thin-layer Chromatographic Identification Tests á201ñ.)
Developing solvent— Prepare a mixture of isopropyl alcohol and toluene (1:1).
Standard solution— Dissolve 20.0mg of USP Ifosfamide RSin 1.0mLof alcohol.
Test solution— Dissolve 20mg of Ifosfamide for Injection in 1.0mLof alcohol.
Procedure— Apply separately 10µLeach of the Standard solutionand the Test solutionto a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture,allow the spots to dry,and develop the plate in a paper-lined chromatographic chamber equilibrated with Developing solventfor about 15minutes prior to use.Allow the chromatogram to develop until the solvent front has moved about 15cm.Remove the plate,mark the solvent front,and air-dry for 5minutes.Place the plates into a chromatographic chamber containing iodine crystals,and view the spots that develop.[NOTE—For better detection,overspray the iodine stain with a mixture of alcohol and water (1:1).]The RFvalue of the principal spot obtained from the Test solutioncorresponds to that obtained from the Standard solution.
B: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that of the Standard preparation,both relative to the internal standard,as obtained in the Assay.
Bacterial endotoxins á85ñ— It contains not more than 0.125USP Endotoxin Unit per mg.
pHá791ñ: between 4.0and 7.0in a solution prepared as directed for Constituted Solutionsunder Injections á1ñ,determined 30minutes after its preparation.
Water,Method Iá921ñ: not more than 0.3%.
Other requirements— It meets the requirements for Sterility Tests á71ñ,Uniformity of Dosage Units á905ñ,and Labelingunder Injections á1ñ.
Assay—
Mobile phase,Internal standard solution,Standard preparation,and Chromatographic system— Prepare as directed in the Assayunder Ifosfamide.
Assay preparation— Select an accurately counted number of containers of Ifosfamide for Injection,the combined contents of which are equivalent to about 6g of Ifosfamide.Dissolve the contents of each container in water and combine all of the solutions in a 1000-mLvolumetric flask.Rinse each container with water,and add the rinsings to the volumetric flask.Dilute with water to volume,and mix.Transfer 10.0mLof the resulting solution to a 100-mLvolumetric flask,add 4.0mLof Internal standard solution,dilute with water to volume,and mix.
Procedure— Proceed as directed for Procedurein the Assayunder Ifosfamide.Calculate the quantity,in g,of C7H15Cl2N2O2Pin each container of Ifosfamide for Injection taken by the formula:
10(C/N)(RU/RS),
in which Cis the concentration,in mg per mL,of USP Ifosfamide RSin the Standard preparation,Nis the number of containers selected for the Assay preparation,and RUand RSare the ratios of the responses of the ifosfamide peak to the ethylparaben peak 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 999
Phone Number:1-301-816-8389