Mitomycin
;)
Azirino[2¢,3¢:3,4]pyrrolo[1,2-a]indole-4,7-dione,6-amino-8-[[(aminocarbonyl)oxy]methyl]-1,1a,2,8,8a,8b-hexahydro-8a-methoxy-5-methyl-,[1aR-(1aa,8b,8aa,8ba)]-.
6-Amino-1,1a,2,8,8a,8b-hexahydro-8-(hydroxymethyl)-8a-methoxy-5-methylazirino[2¢,3¢:3,4]-pyrrolo[1,2-a]indole-4,7-dione carbamate (ester).
Mitomycin C [50-07-7].
»Mitomycin has a potency of not less than 970µg of C15H18N4O5per mg.
Packaging and storage—
Preserve in tight,light-resistant containers.Store at 25
,excursion permitted between 15and 30.
,excursion permitted between 15and 30.
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 á197Mñ—Do not dry specimens.
B:Ultraviolet Absorption á197Uñ—
Solution:
5µg per mL.
Medium:
methanol.
Absorptivity at 357nm is not less than 95.0%and not more than 105.0%of USP Mitomycin RS,calculated on the anhydrous basis.
Crystallinity á695ñ:
meets the requirements.
pHá791ñ:
between 6.0and 7.5,in an aqueous suspension containing 5mg per mL.
Water,Method Iá921ñ:
not more than 2.5%.
Other requirements—
Where the label states that Mitomycin is sterile,it meets the requirements of the tests for Sterilityand Bacterial endotoxins under Mitomycin for Injection.Where the label states that Mitomycin must be subjected to further processing during the preparation of injectable dosage forms,it meets the requirements of the test for Bacterial endotoxins under Mitomycin for Injection.
Assay—
Mobile phase—
Dissolve 1.54g of ammonium acetate in 250mLof methanol,add 5.0mLof 0.83Nacetic acid and water to make 1000mL,and mix.Pass through a filter having a 0.5-µm or finer porosity,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation—
Quantitatively dissolve an accurately weighed quantity of USP Mitomycin RSin N,N-dimethylacetamide to obtain a solution having a known concentration of about 0.5mg per mL.
Resolution solution—
Dissolve suitable quantities of USP Mitomycin RSand 3-ethoxy-4-hydroxybenzaldehyde in N,N-dimethylacetamide to obtain a solution containing about 0.5mg and 7.5mg per mL,respectively.
Assay preparation—
Transfer about 25mg of Mitomycin,accurately weighed,to a 50-mLvolumetric flask,add N,N-dimethylacetamide to volume,and mix to dissolve.
Chromatographic system(see Chromatography á621ñ)—
The liquid chromatograph is equipped with a 365-nm detector and a 4-mm ×30-cm column that contains packing L11.The flow rate is about 2mLper minute.Chromatograph the Resolution solution,and record the peak responses as directed under Procedure:the resolution,R,between the mitomycin and the 3-ethoxy-4-hydroxybenzaldehyde peaks is not less than 1.8.The relative retention times are about 1.0for mitomycin and 1.4for 3-ethoxy-4-hydroxybenzaldehyde.Chromatograph the Standard preparation,and record the peak responses as directed forProcedure:the tailing factor for the mitomycin peak is not more than 1.3;and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the areas for the major peaks.Calculate the quantity,in µg,of C15H18N4O5in each mg of the Mitomycin taken by the formula:
50(CP/W)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Mitomycin RSin the Standard preparation;Pis the stated potency,in µg per mg,of the USP Mitomycin RS;Wis the weight,in mg,of Mitomycin taken to prepare the Assay preparation;and rUand rSare the peak areas 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 1301
Pharmacopeial Forum:Volume No.29(4)Page 1052
Phone Number:1-301-816-8335