Development and Validation of an Uplc Method for In-vitro Study of Glipizide Extended Release Tablets

A Reversed Phase Ultra Performance Liquid Chromatographic (RP-UPLC) method was developed for the determination of glipizide (GLI) in in-vitro study during formulation development. The chromatographic separation was achieved on a Acquity UPLC BEH C18 (50 mm × 2.1 mm, 1.7 μm) column, with a mixture of 55 volumes of methanol and 45 volumes of buffer contain 0.001M sodium dihydrogen phosphate in isocratic elution with flow rate of 0.3 mL/min. The eluted compound was monitored at a wavelength of 276 nm using a UV detector. The method described herein separated glipizide and glipizide related compound-A from all other formulation components within a run time of 1.2 min. The RP-HPLC method was developed and validated according to the International Conference on Harmonization (ICH) guidelines. This method was successfully applied in the quantitative determination of glipizide in in-vitro study during formulation development. The procedure described herein is simple, selective, and reliable for routine quality control analysis as well as stability testing. INTRODUCTION: Glipizide (GLI) is an oral medium-tolong acting anti-diabetic drug from the sulfonylurea class. It is classified as a second generation sulfonylurea, which means that it undergoes enterohepatic circulation. The structure on the R2 group is a much larger cyclo or aromatic group compared to the 1st generation sulfonylureas. This leads to a once a day dosing that is much less than the first generation, about 100 fold. Mechanism of action is produced by blocking potassium channels in the beta cells of the islets of Langerhans. By partially blocking the potassium channels, it will increase the time the cell spends in the calcium release stage of cell signaling leading to an increase in calcium. The increase in calcium will initiate more insulin release from each beta cell . GLI is a salt with pKa of 5.9. It is insoluble in water and alcohols, but soluble in 0.1 N NaOH; it is freely soluble in dimethylformamide . Related compound-A is the major degradation product of GLI . FIG. 1: (A) STRUCTURE OF GLIPIZIDE AND (B)GLIPIZIDE RELATED COMPOUND-A