Tolbutamide
;)
Benzenesulfonamide,N-[(butylamino)carbonyl]-4-methyl-.
1-Butyl-3-(p-tolylsulfonyl)urea [64-77-7].
»Tolbutamide contains not less than 97.0percent and not more than 103.0percent of C12H18N2O3S,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers.
Labeling—
Where it is intended for use in preparing injectable dosage forms,the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms.
Identification,
Infrared Absorption á197Mñ.
Loss on drying á731ñ—
Dry it at 105
for 3hours:it loses not more than 0.5%of its weight.
for 3hours:it loses not more than 0.5%of its weight.
Selenium á291ñ:
0.003%,a 100-mg specimen,mixed with 100mg of magnesium oxide,being used.
Heavy metals,Method IIá231ñ:
0.002%.
Limit of non-sulfonyl urea—
Dissolve 500mg in 10mLof 0.5Nammonium hydroxide:not more than a faint opalescence occurs.
Organic volatile impurities,Method IVá467ñ:
meets the requirements.
Other requirements—
Where the label states that Tolbutamide is sterile,it meets the requirements for Sterility Tests á71ñand for Bacterial endotoxinsunder Tolbutamide for Injection.Where the label states that Tolbutamide must be subjected to further processing during the preparation of injectable dosage forms,it meets the requirements for Bacterial endotoxinsunder Tolbutamide for Injection.
Assay—
Mobile phase—
Prepare a filtered and degassed mixture of hexane,water-saturated-hexane,tetrahydrofuran,alcohol,and glacial acetic acid (475:475:20:15:9).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Internal standard solution—
Dissolve a suitable quantity of tolazamide in alcohol-free chloroform to obtain a solution containing about 3mg per mL.
Standard preparation—
Dissolve an accurately weighed quantity of USP Tolbutamide RSin Internal standard solutionto obtain a solution having a known concentration of about 1.5mg per mL.
Assay preparation—
Transfer about 15mg of Tolbutamide,accurately weighed,to a 10-mLvolumetric flask.Dissolve in and dilute with Internal standard solutionto volume,and mix.
Chromatographic system
(see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 4.0-mm ×30-cm column that contains packing L3.The flow rate is about 1.5mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 2.0%,and the resolution,R,between tolbutamide and tolazamide is not less 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.The relative retention times are about 0.6for tolbutamide and 1.0for tolazamide.Calculate the quantity,in mg,of C12H18N2O3Sin the portion of Tolbutamide taken by the formula:
10C(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 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
Pharmacopeial Forum:Volume No.29(5)Page 1588
Phone Number:1-301-816-8251