Isoxsuprine Hydrochloride Injection
»Isoxsuprine Hydrochloride Injection is a sterile solution of Isoxsuprine Hydrochloride in Water for Injection.It contains not less than 95.0percent and not more than 105.0percent of the labeled amount of C18H23NO3·HCl.
Packaging and storage— Preserve in single-dose or in multiple-dose containers,preferably of Type Iglass.
Identification— To a 60-mLseparator transfer 10mLof pH9.0buffer (prepared by mixing equal volumes of 0.1Mmonobasic potassium phosphate and 0.1Nsodium hydroxide and,using a pHmeter,adjusting to a pHof 9.0by adding,as necessary,more of either solution)add 1mLof Injection,and mix.Add 2mLof chloroform,shake vigorously for 1minute,filter the chloroform extract through a pledget of cotton,and mix the filtrate with 500mg of potassium bromide.Evaporate the chloroform,carefully removing the last trace of solvent in a small vacuum flask:the IRabsorption spectrum of a potassium bromide dispersion of the isoxsuprine so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Isoxsuprine Hydrochloride RSthat has been treated in the same manner.
Bacterial endotoxins á85ñ— It contains not more than 35.70USP Endotoxin Units per mg of isoxsuprine hydrochloride.
pHá791ñ: between 4.9and 6.0.
Other requirements— It meets the requirements under Injections á1ñ.
Assay—
pH4.0citrate buffer— Mix equal volumes of 0.5Mcitric acid and 0.5Msodium citrate,and adjust,by the addition of either solution as necessary,the pHof the solution to 4.0±0.2.
Mixed solvent— Shake 40mLof ether,160mLof isooctane,and 10mLof water in a separator,remove and discard the water phase,and pass the solvent phase through a large pledget of cotton to remove excess water.
Standard preparation— Transfer about 40mg of USP Isoxsuprine Hydrochloride RS,accurately weighed,to a 50-mLvolumetric flask,add 2Nsulfuric acid to volume,and mix.Transfer 10.0mLof this solution to a 100-mLvolumetric flask,dilute with 2Nsulfuric acid to volume,and mix.The concentration of USP Isoxsuprine Hydrochloride RSin the Standard preparationis about 80µg per mL.
Chromatographic column— Proceed as directed under Column Partition Chromatography(see Chromatography á621ñ),packing a chromatographic tube with two segments of packing material.The lower segment is a mixture of 2g of Solid Supportand 1mLof pH4.0citrate buffer,and the upper segment is a mixture prepared as directed under Assay preparation.
Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 4mg of isoxsuprine hydrochloride,to a 100-mLbeaker,add 1mLof dimethyl sulfoxide,and allow to stand for about 10minutes,with occasional swirling.Add 1mLof pH4.0citrate bufferand 3g of Solid Support,mix as directed under Chromatographic column,and transfer to the column.Pass 75mLof Mixed solventthrough the column,and discard the eluate.Elute the column with a solution prepared by mixing 0.2mLof bis(2-ethylhexyl)phosphoric acid with 75mLof Mixed solvent,and collect the eluate in a 125-mLseparator.Extract the eluate with two 20-mLportions of 2Nsulfuric acid.Transfer the extracts to a 50-mLvolumetric flask,dilute with 2Nsulfuric acid to volume,and mix.
Procedure— Concomitantly determine the absorbances of the Assay preparationand the Standard preparationin 1-cm cells at the wavelength of maximum absorbance at about 275nm,with a suitable spectrophotometer,using a column blank,prepared with Mixed solvent,to set the instrument.Calculate the quantity,in mg,of C18H23NO3·HCl in the portion of Injection taken by the formula:
0.05C(AU/AS),
in which Cis the concentration,in µg per mL,of USP Isoxsuprine Hydrochloride RSin the Standard preparation,and AUand ASare the absorbances of 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 1090
Phone Number:1-301-816-8305