»Miconazole Injection is a sterile solution of Miconazole in Water for Injection.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of miconazole (C18H14Cl4N2O).
Packaging and storage Preserve in single-dose containers,preferably of Type Iglass,at controlled room temperature.
Dragendorff's reagent Dissolve 0.85g of bismuth subnitrate in a mixture of 40mLof water and 10mLof glacial acetic acid (Solution A).Dissolve 8g of potassium iodide in 20mLof water (Solution B).Transfer 5mLof Solution A,5mLof Solution B,and 20mLof glacial acetic acid to a 100-mLvolumetric flask,dilute with water to volume,and mix.
Procedure Transfer a volume of Injection,equivalent to about 50mg of miconazole,to a 10-mLvolumetric flask,dilute with methanol to volume,and mix.Dissolve a suitable quantity of USP Miconazole RSin methanol to obtain a Standard solution having a known concentration of about 5mg per mL.Apply separate 5-µLportions of the two solutions to the starting line of a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Develop the chromatogram in a suitable chamber with a freshly prepared solvent system consisting of a mixture of n-hexane,chloroform,methanol,and ammonium hydroxide (60:30:10:1)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the chamber,and allow the solvent to evaporate.Locate the spots on the plate by spraying with Dragendorff's reagent:the RFvalue of one of the principal spots obtained from the test solution corresponds to that obtained from the Standard solution.
Bacterial endotoxins á85ñ It contains not more than 0.10USP Endotoxin Unit per mg of miconazole.
pHá791ñ: between 3.7and 5.7.
Particulate matter á788ñ: meets the requirements under small-volume injections.
Other requirements It meets the requirements under Injections á1ñ.
Mobile phase Dissolve 5.0g of ammonium acetate in 200mLof water,add 300mLof acetonitrile and 500mLof methanol,mix,filter,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation Dissolve an accurately weighed quantity of USP Miconazole RSin Mobile phaseand dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having a known concentration of about 0.5mg per mL.Transfer 10.0mLof this solution to a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix to obtain a Standard preparationhaving a known concentration of about 50µg per mL.
Resolution solution Dissolve suitable quantities of USP Miconazole RSand dibutyl phthalate in Mobile phaseto obtain a solution containing about 50µg of each per mL.
Assay preparation Transfer an accurately measured volume of Injection,equivalent to about 50mg of miconazole,to a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.Transfer 10.0mLof this solution to a 100-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ)The liquid chromatograph is equipped with a 230-nm detector and a 4.6-mm ×30-cm column that contains packing L7.The flow rate is about 2mLper minute.Chromatograph the Resolution solutionand the Standard preparation,and record the peak responses as directed under Procedure:the resolution,R,between the dibutyl phthalate and miconazole peaks is not less than 5.0,the tailing factor for the miconazole peak is not more than 1.3,and the relative standard deviation for replicate injections of the Standard preparationis not more than 2.0%.The relative retention times are about 0.7for dibutyl phthalate and 1.0for miconazole.
Procedure [NOTEAllow the chromatograph to run for at least 16to 18minutes between injections to allow for elution of all components associated with the Injection vehicle.]Separately inject equal volumes (about 20µL)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 miconazole (C18H14Cl4N2O)in each mLof the Injection taken by the formula:
(C/V)(rU/rS),in which Cis the concentration,in µg per mL,of USP Miconazole RSin the Standard preparation,Vis the volume,in mL,of Injection taken,and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information Staff Liaison:Behnam Davani,Ph.D.,MBA,Senior Scientist
Expert Committee:(PA7)Pharmaceutical Analysis 7