Dipyridamole Injection
»Dipyridamole Injection is a sterile solution of Dipyridamole in Water for Injection.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of dipyridamole (C24H40N8O4).
Packaging and storage— Preserve in Containers for Injectionsas described underInjections á1ñ.Protect from light,and avoid freezing.
Identification—
A:Thin-Layer Chromatographic Identification Test á201ñ—
Test solution— Use the Injection.
Standard solution: 5mg per mLin a mixture of methanol,water,and 0.1Nhydrochloric acid (5:4:1).
Developing solvent system: a mixture of butyl alcohol,water,and glacial acetic acid (34:10:5).
Procedure— Proceed as directed in the chapter.Locate the yellow spots on the plate:the RFvalue of the principal spot obtained from the Test solutioncorresponds to that of the principal spot obtained from the Standard solution.Spray the plate lightly with a spray reagent prepared as follows.Transfer 1g of iodine and 3g of potassium iodide to a 100-mLvolumetric flask.Add 10mLof alcohol to dissolve (heat gently).Add 20mLof 2Nsulfuric acid,dilute with water to volume,and mix.Store in a dark place.Observe the plate,and locate the brown spots:the RFvalue of the principal spot obtained from the Test solutioncorresponds to that of the principal spot obtained from the Standard solution.
B: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.
Bacterial endotoxins á85ñ— It contains not more than 8.8USP Endotoxin Units per mg of dipyridamole.
pHá791ñ: between 2.2and 3.2.
Chromatographic purity— [NOTE—Protect dipyridamole solutions from exposure to light.]
Mobile phaseandChromatographic system— Proceed as directed in the Assay.
Test solution— Use the Assay preparationprepared as directed in the Assay.
Procedure— Inject a volume (about 10µL)of the Test solutioninto the chromatograph,record the chromatogram,and measure the peak responses.Calculate the percentage of each impurity in the portion of Injection taken by the formula:
100(ri/rs),
in which riis the peak response for each impurity;and rsis the sum of the responses of all of the peaks:not more than 2.0%of any individual impurity is found;and not more than 4.5%of total impurities is found.
Other requirements— It meets the requirements under Injections á1ñ.
Assay— [NOTE—Protect dipyridamole solutions from exposure to light.]
Acetate buffer— Dissolve a quantity of sodium acetate in water to obtain a concentration of about 6.8mg per mL.Adjust with acetic acid to a pHof 5.1±0.1.
Mobile phase— Prepare a filtered and degassed mixture of methanol and Acetate buffer(65:35).Make adjustments if necessary (see System Suitability underChromatography á621ñ).
Standard preparation— Dissolve an accurately weighed quantity of USP Dipyridamole RSin Mobile phase,and dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having a known concentration of about 1.0mg per mL.
Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 25mg of dipyridamole,to a 25-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 276-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1.0mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency is not less than 2000theoretical plates;the tailing factor is not greater than 1.7;and the relative standard deviation for replicate injections is not greater 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 responses for the major peaks.Calculate the quantity,in mg,of dipyridamole (C24H40N8O4)in the portion of Injection taken by the formula:
25C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Dipyridamole RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 674
Pharmacopeial Forum:Volume No.28(4)Page 1105
Phone Number:1-301-816-8305