Flunisolide Nasal Solution
»Flunisolide Nasal Solution is an aqueous,buffered solution of Flunisolide.It is supplied in a form suitable for nasal administration.It contains not less than 90.0percent and not more than 110.0percent of the labeled amount of C24H31FO6.
Packaging and storage— Preserve in tight containers,protected from light,and store at controlled room temperature.
Identification— Proceed as directed in the Assay,except to inject 50µLto 200µLof a mixture of the Assay preparationand the Standard preparation(1:1)onto the column,adjusting the response to obtain a response that is between 50%and 90%full scale:a single peak is observed in the chromatogram for the mixed solution.
pHá791ñ: between 4.5and 6.0,a silver-silver chloride (internal element)electrode being used in conjunction with a fiber junction calomel electrode.
Quantity delivered per spray— Prime the spray pump by delivering 10sprays into a fume hood.Accurately weigh the entire assembly,record the weight,and deliver 8more sprays into the hood.Again weigh the assembly,and record the weight.Calculate the quantity,in µg,of C24H31FO6delivered per spray taken by the formula:
[(W1-W2)/8][A/D],
in which W1and W2are the first and second weights,respectively,in g;Ais the quantity,in µg per mL,of C24H31FO6found in the Assay;and Dis the density of Nasal Solution,in g per mL.The quantity delivered is between 17µg and 33µg per spray.
Assay—
Mobile phase— Prepare a suitable degassed solution of water,acetonitrile,and glacial acetic acid (69:30:1to 64:35:1).Adjust the ratio as necessary to obtain suitable chromatographic performance.
Internal standard solution— Dissolve norethindrone in acetonitrile to obtain a solution containing about 300µg per mL.
Standard preparation— Dissolve an accurately weighed quantity of USP Flunisolide RSin a mixture of acetonitrile and Mobile phase(1:1)to obtain a solution having a known concentration of about 250µg per mL.Transfer 1.0mLof this solution,and 1.0mLof Internal standard solution,by means of “to contain”pipets,to a 50-mLvolumetric flask.Rinse the pipets with Mobile phase,adding the rinsings to the flask,dilute with Mobile phaseto volume,and mix.The final concentration of USP Flunisolide RSis about 5µg per mL.
Assay preparation— Transfer an accurately measured volume of Nasal Solution,equivalent to about 250µg of flunisolide,to a 50-mLvolumetric flask,and add 1.0mLof Internal standard solutionby means of “to contain”pipets.Rinse the pipets with Mobile phase,adding the rinsing to the flask,dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 4-mm ×25-cm column that contains 5-to 10-µm packing L1.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the resolution,R,between the analyte and the internal standard is not less than 5.0;and the relative standard deviation for replicate injections is not more than 1.5%.
Procedure— Separately inject equal volumes (about 50µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.The relative retention times are about 0.6for flunisolide and 1.0for norethindrone.Calculate the quantity,in mg,of C24H31FO6in each mLof the Nasal Solution taken by the formula:
(434.51/443.51)(50C/V)(RU/RS),
in which 434.51and 443.51are the molecular weights of C24H31FO6and C24H31FO6·½H2O,respectively;Cis the concentration,in mg per mL,of USP Flunisolide RSin the Standard preparation;Vis the volume,in mL,of Nasal Solution taken;and RUand RSare the peak response ratios of the flunisolide peak and the norethindrone peak obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 836
Phone Number:1-301-816-8139