Tolbutamide Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Tolbutamide Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of tolbutamide (C₁₂H₁₈N₂O₃S).

2 IDENTIFICATION

Delete the following:

Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M

Sample solution: Triturate a quantity of finely powdered Tablets, equivalent to 500 mg of tolbutamide, with 50 mL of chloroform, and filter. Evaporate the clear filtrate on a steam bath to dryness.

Add the following:

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

Add the following:

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Buffer: 1.36 g/L of potassium phosphate, monobasic in water. Adjust with phosphoric acid to a pH of 3.5.

Mobile phase: Acetonitrile and Buffer (35:65)

Diluent: Acetonitrile and Buffer (70:30)

System suitability solution: 1 mg/mL of USP Tolbutamide RS and 10 µg/mL of USP Tolazamide RS in Diluent

Standard solution: 0.1 mg/mL of USP Tolbutamide RS in Diluent

Sample stock solution: Nominally 0.2 mg/mL of tolbutamide from Tablets in Diluent prepared as follows. Transfer a quantity equivalent to 50 mg of tolbutamide, from finely powdered Tablets (NLT 5), to a 250-mL volumetric flask containing 150 mL of Diluent. Shake by mechanical means for NLT 30 min, and dilute with Diluent to volume.

Sample solution: Nominally 0.1 mg/mL of tolbutamide from the Sample stock solution in Diluent. Let stand for NLT 10 min and analyze the supernatant.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 230 nm. For Identification A, use a diode array detector in the range of 210–400 nm.
• Column: 4.6-mm × 25-cm; 5-µm packing L1
• Autosampler temperature: 4°
• Flow rate: 1.5 mL/min
• Injection volume: 30 µL
• Run time: NLT 1.5 times the retention time of tolbutamide

System suitability

• Samples: System suitability solution and Standard solution
• Suitability requirements
• Resolution: NLT 2.0 between tolbutamide and tolazamide, System suitability solution
• Tailing factor: NMT 2.0, Standard solution
• Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of tolbutamide (C₁₂H₁₈N₂O₃S) in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of tolbutamide from the Sample solution

rₛ = peak response of tolbutamide from the Standard solution

Cₛ = concentration of USP Tolbutamide RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of tolbutamide in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

Medium: pH 7.4 phosphate buffer; 900 mL

Apparatus 2: 75 rpm

Time: 30 min

Standard solution: USP Tolbutamide RS prepared in a similar manner as the Sample solution

[Note-An amount of alcohol not to exceed 1% of the total volume of the Standard solution may be used to bring the Reference Standard into solution before dilution with Medium.]

Sample solution: Pass a portion of the solution under test through a suitable filter. Dilute with water as needed.

Instrumental conditions

• (See Ultraviolet-Visible Spectroscopy 〈857〉.)
• Mode: UV-Vis
• Analytical wavelength: UV 226 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of tolbutamide (C₁₂H₁₈N₂O₃S) dissolved:

Result = (Aᵤ/Aₛ) × Cₛ × V × (1/L) × D × 100

Aᵤ = absorbance of the Sample solution

Aₛ = absorbance of the Standard solution

Cₛ = concentration of USP Tolbutamide RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

D = dilution factor of the Sample solution, as needed

Tolerances: NLT 70% (Q) of the labeled amount of tolbutamide (C₁₂H₁₈N₂O₃S) is dissolved.

4.2 Uniformity of Dosage Units 〈905〉

Meet the requirements

5 IMPURITIES

5.1 Organic Impurities

Buffer, Mobile phase, Diluent, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 0.002 mg/mL of USP Tolbutamide RS in Diluent

Sensitivity solution: 0.5 µg/mL of USP Tolbutamide RS in Diluent from the Standard solution

Sample solution: Nominally 1 mg/mL of tolbutamide from Tablets in Diluent as follows. Transfer a quantity equivalent to 250 mg of tolbutamide, from finely powdered Tablets (NLT 5), to a 250-mL volumetric flask containing 150 mL of Diluent. Shake by mechanical means for NLT 30 min, and dilute with Diluent to volume. Let stand for NLT 10 min and analyze the clear supernatant.

System suitability

• Samples: System suitability solution, Standard solution, and Sensitivity solution
• [Note-The relative retention times for tosylurea, tolbutamide, and tolazamide are 0.21, 1.00, and 1.14, respectively.]
• Suitability requirements
• Resolution: NLT 2.0 between tolbutamide and tolazamide, System suitability solution
• Tailing factor: NMT 2.0, Standard solution
• Relative standard deviation: NMT 5.0%, Standard solution
• Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each degradation product in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × (1/F) × 100

rᵤ = peak response of each degradation product from the Sample solution

rₛ = peak response of tolbutamide from the Standard solution

Cₛ = concentration of USP Tolbutamide RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of tolbutamide in the Sample solution (mg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. The reporting threshold is 0.05%.

Table 1

ᵃ 4-Methylbenzenesulfonamide.

6 ADDITIONAL REQUIREMENTS

Change to read:

Packaging and Storage: Preserve in well-closed containers. Store at controlled room temperature and protect from light.

Change to read:

USP Reference standards 〈11〉

USP Tolazamide RS

USP Tolbutamide RS