Tolbutamide for Injection
»Tolbutamide for Injection is prepared from Tolbutamide with the aid of Sodium Hydroxide.It contains an amount of tolbutamide sodium equivalent to not less than 95.0percent and not more than 105.0percent of the labeled amount of tolbutamide (C12H18N2O3S).
Packaging and storage— Preserve in Containers for Sterile Solidsas described under Injections á1ñ.
Constituted solution— At the time of use,it meets the requirements for Constituted Solutionsunder Injections á1ñ.
Identification,Infrared Absorption á197Mñ— Obtain the test specimen as follows.Place about 200mg in a suitable container,dissolve in about 20mLof water,add 2mLof 2Nsulfuric acid,and extract with 10mLof chloroform.Filter,and evaporate an aliquot of the chloroform layer.Dry the residue at 105for 3hours.Use USP Tolbutamide RSas the standard for comparison.
Bacterial endotoxins á85ñ— It contains not more than 0.35USP Endotoxin Unit per mg of tolbutamide sodium.
pHá791ñ: between 8.0and 9.8,in a solution containing 50mg per mL.
Loss on drying á731ñ— Dry it at 105for 4hours:it loses not more than 1.0%of its weight.
Other requirements— It meets the requirements for Sterility Tests á71ñ,Uniformity of Dosage Units á905ñ,and Labelingunder Injections á1ñ.
Assay—
Mobile phase and Chromatographic system—Prepare as directed in the Assayunder Tolbutamide.
Internal standard solution— Prepare a solution of tolazamide in alcohol-free chloroform containing about 15mg per mL.
Diluting solution— Prepare an alcohol-free chloroform solution containing 3%(v/v)of glacial acetic acid.
Standard preparation— Dissolve an accurately weighed quantity of USP Tolbutamide RSin Internal standard solutionto obtain a known concentration of about 7.5mg per mL.Add Diluting solutionto obtain a Standard preparationhaving a final known concentration of about 1.5mg of tolbutamide per mL.
Assay preparation— Add about 15mLof water to 1container of Tolbutamide for Injection,and shake vigorously to dissolve the contents.Transfer the contents,using adequate rinsing with water,to a 50-mLvolumetric flask.Dilute with water to volume,and mix.Transfer an accurately measured portion of this solution,equivalent to about 75mg of tolbutamide,to a 50-mLvolumetric flask,add 10.0mLof Internal standard solution,and dilute with Diluting solutionto volume.Shake vigorously for about 15minutes,and centrifuge or allow to stand for about 15minutes.Use the lower,clear layer,as the Assay preparation.
Procedure— 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.The relative retention times are about 0.6for tolbutamide and 1.0for tolazamide.Calculate the quantity,in mg,of C12H18N2O3Sin the portion of solution taken for the Assay preparationby the formula:
50C(RU/RS),
in which Cis the concentration,in mg per mL,of USP Tolbutamide RSin the Standard preparation,and RUand RSare the peak response ratios of the tolbutamide and internal standard peaks obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(PA4)Pharmaceutical Analysis 4
USP28–NF23Page 1948
Phone Number:1-301-816-8251