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Tolbutamide
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C12H18N2O3S 270.35

Benzenesulfonamide, N-[(butylamino)carbonyl]-4-methyl-.
1-Butyl-3-(p-tolylsulfonyl)urea [64-77-7].
» Tolbutamide contains not less than 97.0 percent and not more than 103.0 percent 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 197M.
Melting range 741: between 126 and 130.
Loss on drying 731— Dry it at 105 for 3 hours: it loses not more than 0.5% of its weight.
Selenium 291: 0.003%, a 100-mg specimen, mixed with 100 mg of magnesium oxide, being used.
Heavy metals, Method II 231: 0.002%.
Limit of non-sulfonyl urea— Dissolve 500 mg in 10 mL of 0.5 N ammonium hydroxide: not more than a faint opalescence occurs.
Organic volatile impurities, Method IV 467: meets the requirements.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Other requirements— Where the label states that Tolbutamide is sterile, it meets the requirements for Sterility Tests 71 and for Bacterial endotoxins under 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 endotoxins under 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 Suitability under Chromatography 621).
Internal standard solution— Dissolve a suitable quantity of tolazamide in alcohol-free chloroform to obtain a solution containing about 3 mg per mL.
Standard preparation— Dissolve an accurately weighed quantity of USP Tolbutamide RS in Internal standard solution to obtain a solution having a known concentration of about 1.5 mg per mL.
Assay preparation— Transfer about 15 mg of Tolbutamide, accurately weighed, to a 10-mL volumetric flask. Dissolve in and dilute with Internal standard solution to volume, and mix.
Chromatographic system (see Chromatography 621)—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 1.5 mL per 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 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The relative retention times are about 0.6 for tolbutamide and 1.0 for tolazamide. Calculate the quantity, in mg, of C12H18N2O3S in the portion of Tolbutamide taken by the formula:
10C(RU / RS),
in which C is the concentration, in mg per mL, of USP Tolbutamide RS in the Standard preparation, and RU and RS are the peak response ratios obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Elena Gonikberg, Ph.D., Scientist
Expert Committee : (MDGRE05) Monograph Development-Gastrointestinal Renal and Endocrine
USP29–NF24 Page 2169
Pharmacopeial Forum : Volume No. 29(5) Page 1588
Phone Number : 1-301-816-8251