Glyburide

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

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

DOWNLOAD PDF HERE

C₂₃H₂₈CIN₃O₅S 494.00

Benzamide, 5-chloro-N-[2-[4-[[[(cyclohexylamino)carbon yl)amino]-sulfonyl]phenyl]ethyl]-2-methoxy-.

1-[[p-[2-(5-Chloro-o-anisamido)ethyl]phenyl]sulfonyl]-3-cyclohexylurea (ERR 1-Jul-2021) CAS RN^®: 10238-21-8; UNII: SX6K58TVWC.

>> Glyburide contains not less than 98.0 percent and not more than 102.0 percent of C₂₃H₂₈CIN₃O₅S, calculated on the dried basis.

1 Packaging and storage

Preserve in tight containers.

2 USP REFERENCE STANDARDS (11)

USP Glyburide RS

3 Identification

A: Spectroscopic Identification Tests (197), Infrared Spectroscopy: 197M.

B: The chromatogram of the Assay preparation obtained as directed in the Assay exhibits a major peak for glyburide, the retention time of which corresponds to that exhibited in the chromatogram of the Standard preparation, both relative to the internal standard, as obtained in the Assay.

3.1 Loss on drying

Dry it at 105° for 6 hours: it loses not more than 1.0% of its weight.

3.2 RESIDUE ON IGNITION (281)

Not more than 0.5%.

4 Chromatographic purity

4.1 Mobile phase

Prepare as directed in the Assay.

4.2 Test solution

To about 10 mg of Glyburide, accurately weighed, add 10 mL of acetonitrile, and shake to dissolve. Add 4 mL of water, and mix.

4.3 Chromatographic system

The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm x 25-cm column that contains packing L7. The flow rate is about 2 mL per minute. Chromatograph the Test solution, and record the peak responses as directed for Procedure: the column efficiency is not less than 3500 theoretical plates.

4.4 Procedure

Inject a volume (about 20 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the areas for the major peaks. Calculate the percentage of each impurity in the portion of Glyburide taken by the formula:

100(r_i/r_S)

5 in which r_i is the peak response for each impurity; and r_S is the sum of the responses of all of the peaks: not more than 1.5% of any impurity, which elutes before glyburide, is found; not more than 0.5% of any other individual impurity is found; and not more than 2.0% of total impurities is found.

5 Assay

5.1 Mobile phase

Dissolve 2.6 g of monobasic ammonium phosphate in 450 mL of water. Add 550 mL of acetonitrile, filter, and degas. Adjust, if necessary, with phosphoric acid or sodium hydroxide to a pH of 5.25 ± 0.30. Make adjustments if necessary (see System Suitability, under Chromatography (621)).

5.2 Internal standard solution

Dissolve Progesterone in acetonitrile to obtain a solution containing about 0.2 mg per mL.

5.3 Standard preparation

To about 10 mg of USP Glyburide RS, accurately weighed, add 20.0 mL of Internal standard solution, and shake vigorously to dissolve. Add 4.0 mL of water, and mix.

5.4 Assay preparation

To about 10 mg of Glyburide, accurately weighed, add 20.0 mL of Internal standard solution, and shake vigorously to dissolve. Add 4.0 mL of water, and mix.

5.5 Chromatographic system (see Chromatography (621))

The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm x 25-cm column that contains packing L7. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.4 for glyburide and 1.0 for progesterone; the resolution, R, between glyburide and progesterone is not less than 5.0; and the relative standard deviation for replicate injections is not more than 2.0%.

5.6 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 heights for the major peaks. Calculate the quantity, in mg, of C₂₃H₂₈CIN₃O₅S in the portion of Glyburide taken by the formula:

W_S(R_U/R_S)

in which W_S is the weight, in mg, of USP Glyburide RS taken to prepare the Standard preparation; and R_U and R_S are the peak height ratios obtained from the Assay preparation and the Standard preparation, respectively.