Methotrexate for Injection
»Methotrexate for Injection is a sterile,freeze-dried preparation of methotrexate sodium with or without suitable added substances,buffers,and/or diluents.It contains not less than 95.0percent and not more than 115.0percent of the labeled amount of methotrexate (C20H22N8O5).
Caution—Great care should be taken to prevent inhaling particles of methotrexate sodium and exposing the skin to it.
Packaging and storage— Preserve in Containers for Sterile Solidsas described under Injections á1ñ,protected from light.
Constituted solution— At the time of use,it meets the requirements for Constituted Solutionsunder Injections á1ñ.
Identification— Dissolve a sufficient quantity in water to obtain a solution having a concentration of about 2.5mg per mL.Adjust with 0.1Nhydrochloric acid to a pHof 4.0.Place the slurry in a 50-mLcentrifuge tube,and centrifuge.Decant the supernatant,add 25mLof acetone,shake,and filter through a solvent-resistant,membrane filter having a porosity of 0.45µm.Air-dry the filtered precipitate:the methotrexate so obtained responds to Identificationtest Aunder Methotrexate.
Bacterial endotoxins á85ñ— It contains not more than 0.4USP Endotoxin Unit per mg of methotrexate sodium.
pHá791ñ: between 7.0and 9.0in a solution constituted as directed in the labeling,except that water is used as the diluent.
Other requirements— It meets the requirements for Labelingunder Injections á1ñ,for Sterility Tests á71ñ,and for Uniformity of Dosage Units á905ñ.
Assay—
pH6.0Buffer solution ,Mobile phase,System suitability preparation,System suitability test,and Standard preparation—Proceed as directed in the Assayunder Methotrexate.
Assay preparation— Dissolve the contents of 1container of Methotrexate for Injection in an accurately measured volume of Mobile phaseto obtain a solution having a known concentration of about 0.1mg per mL.
Procedure— Proceed as directed for Procedurein the Assayunder Methotrexate.Calculate the quantity,in mg,of methotrexate (C20H22N8O5)in the container of Methotrexate for Injection taken by the formula:
C(L/D)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Methotrexate RS,corrected for water content,in the Standard preparation;Lis the labeled quantity of Methotrexate in the container;Dis the concentration,in mg per mL,of Methotrexate in the Assay preparationon the basis of the labeled quantity in the container and the extent of dilution;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 1249
Phone Number:1-301-816-8389