Dactinomycin for Injection
»Dactinomycin for Injection is a sterile mixture of Dactinomycin and Mannitol.It contains not less than 90.0percent and not more than 120.0percent of the labeled amount of C62H86N12O16,the labeled amount being 0.5mg in each container.
Caution—Great care should be taken to prevent inhaling particles of Dactinomycin and exposing the skin to it.
Packaging and storage—
Preserve in light-resistant Containers for Sterile Solidsas described under Injections á1ñ.
Labeling—
Label it to include the statement “Protect from light.”
Constituted solution—
At the time of use,it meets the requirements for Constituted Solutionsunder Injections á1ñ.
Identification—
A:
The UVabsorption spectrum of a methanol solution containing about 25µg of dactinomycin per mLexhibits maxima and minima at the same wavelengths as that of a similar solution of USP Dactinomycin RS,concomitantly measured,and the ratio A240/A445is between 1.30and 1.50.
B:
The chromatogram obtained from the Assay preparationin the Assayexhibits a major peak for dactinomycin,the retention time of which corresponds to that exhibited by the Standard preparation,and the chromatogram compares qualitatively to that obtained from the Standard preparation.
Bacterial endotoxins á85ñ—
It contains not more than 100.0USP Endotoxin Units per mg of dactinomycin.
Sterility á71ñ—
It meets the requirements when tested as directed for Membrane Filtrationunder Test for Sterility of the Product To Be Examined,each container being constituted aseptically by injecting Sterile Water for Injection through the stopper,and the entire contents of all the containers being collected aseptically with the aid of 200mLof Fluid Abefore filtering.
pHá791ñ:
between 5.5and 7.5,in the solution constituted as directed in the labeling.
Loss on drying á731ñ—
Dry it in vacuum at a pressure not exceeding 5mm of mercury at 60
for 3hours:it loses not more than 4.0%of its weight.
for 3hours:it loses not more than 4.0%of its weight.
Other requirements—
It meets the requirements under Injections á1ñ.
Assay—
[NOTE—In this procedure,use freshly prepared Standard preparation and Assay preparation,protected from light.]
Mobile phase—
Mix 6volumes of acetonitrile and 4volumes of water,filter through a membrane filter (1-µm or finer porosity),and degas.[NOTE—The acetonitrile concentration may be varied to provide appropriate Chromatographic system performance and to provide a suitable elution time.]
Standard preparation—
Dissolve an accurately weighed quantity of USP Dactinomycin RSin Mobile phase,and dilute quantitatively with Mobile phaseto obtain a solution having a known concentration of about 250µg of dactinomycin per mL.
Assay preparation—
Add an accurately measured volume of Mobile phaseto 1container of Dactinomycin for Injection to obtain a solution containing about 250µg of dactinomycin per mL,and filter,if necessary,to obtain a clear solution.
Chromatographic system
(see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 2.5mLper minute.Chromatograph the Standard preparation,and record the peak response as directed under Procedure:the column efficiency is not less than 1200theoretical plates,the tailing factor is not more than 2,and the relative standard deviation for replicate injections is not more than 3.0%.
Procedure—
Separately inject equal volumes (about 10µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.The retention time is about 6minutes for dactinomycin.Calculate the quantity,in mg,of C62H86N12O16in the container of Dactinomycin for Injection taken by the formula:
(CV/1000)(rU/rS),
in which Cis the concentration,in µg,of dactinomycin in each mLof the Standard preparation,Vis the volume,in mL,of the Assay preparation,and rUand rSare the peak responses of 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 570
Phone Number:1-301-816-8335