U.S. PHARMACOPEIA

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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 95.0 percent and not more than 105.0 percent of the labeled amount of tolbutamide (C12H18N2O3S).
Packaging and storage— Preserve in Containers for Sterile Solids as described under Injections 1.
Constituted solution— At the time of use, it meets the requirements for Constituted Solutions under Injections 1.
Identification, Infrared Absorption 197M— Obtain the test specimen as follows. Place about 200 mg in a suitable container, dissolve in about 20 mL of water, add 2 mL of 2 N sulfuric acid, and extract with 10 mL of chloroform. Filter, and evaporate an aliquot of the chloroform layer. Dry the residue at 105 for 3 hours. Use USP Tolbutamide RS as the standard for comparison.
Bacterial endotoxins 85— It contains not more than 0.35 USP Endotoxin Unit per mg of tolbutamide sodium.
pH 791: between 8.0 and 9.8, in a solution containing 50 mg per mL.
Loss on drying 731— Dry it at 105 for 4 hours: it loses not more than 1.0% of its weight.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Other requirements— It meets the requirements for Sterility Tests 71, Uniformity of Dosage Units 905, and Labeling under Injections 1.
Assay—
Mobile phase and Chromatographic system—Prepare as directed in the Assay under Tolbutamide.
Internal standard solution— Prepare a solution of tolazamide in alcohol-free chloroform containing about 15 mg 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 RS in Internal standard solution to obtain a known concentration of about 7.5 mg per mL. Add Diluting solution to obtain a Standard preparation having a final known concentration of about 1.5 mg of tolbutamide per mL.
Assay preparation— Add about 15 mL of water to 1 container of Tolbutamide for Injection, and shake vigorously to dissolve the contents. Transfer the contents, using adequate rinsing with water, to a 50-mL volumetric flask. Dilute with water to volume, and mix. Transfer an accurately measured portion of this solution, equivalent to about 75 mg of tolbutamide, to a 50-mL volumetric flask, add 10.0 mL of Internal standard solution, and dilute with Diluting solution to volume. Shake vigorously for about 15 minutes, and centrifuge or allow to stand for about 15 minutes. Use the lower, clear layer, as the Assay preparation.
Procedure— Separately inject equal volumes (about 20 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 solution taken for the Assay preparation by the formula:
50C(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 of the tolbutamide and internal standard peaks 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
Phone Number : 1-301-816-8251