Thermoanalytical study of glibenclamide and excipients

Summary Taking into account the problems of desertification and agricultural practices able to provide income to the population at the semi-arid region of North-East Brazil, this work presents the results of the chemical and thermal characterization by TG and DSC of the seed derivatives of Cnidoscolus quercifolius, hereinafter called faveleira, aiming at the application of these materials as an alternative of food source for animals and for the human population at this region. The faveleira seed derivatives present thermodynamic properties similar to the ones of other foods utilized for human use, as well as an acceptable calorific value. According to TG and DSC results, was verified that the faveleira derivatives presents good thermal and oxidative stabilities.     

Metabolic profile of glyburide in human liver microsomes using LC‐DAD‐Q‐TRAP‐MS/MS

The sulfonylurea urea drug glyburide (glibenclamide) is widely used for the treatment of diabetes milletus and gestational diabetes. In previous studies monohydroxylated metabolites were identified and characterized for glyburide in different species, but the metabolite owing to the loss of cyclohexyl ring was identified only in mouse. Glyburide upon incubation with hepatic microsomes resulted in 10 metabolites for human. The current study identifies new metabolites of glyburide along with the hydroxylated metabolites that were reported earlier. The newly identified drug metabolites are dihydroxylated metabolites, a metabolite owing to the loss of cyclohexyl ring and one owing to hydroxylation with dehydrogenation. Among the 10 identified metabolites, there were six monohydroxylated metabolites, one dihydroxylated metabolite, two metabolites owing to hydroxylation and dehydrogenation, and one metabolite owing to the loss of cyclohexyl ring. New metabolites of glyburide were identified and characterized using liquid chromatography–diode array detector–quadruple‐ion trap–mass spectrometry/mass spectrometry (LC‐DAD‐Q‐TRAP‐MS/MS). An enhanced mass scan–enhanced product ion scan with information‐dependent acquisition mode in a Q‐TRAP‐MS/MS system was used to characterize the metabolites. Liquid chromatography with diode array detection was used as a complimentary technique to confirm and identify the metabolites. Metabolites formed in higher amounts were detected in both diode array detection and mass spectrometry detection. Copyright © 2012 John Wiley & Sons, Ltd.     

Solid-state characterization of glyburide-cyclodextrin co-ground products

Natural crystalline (α-, β-, γ-) and amorphous derivative (hydroxypropyl-β- and methyl-β) cyclodextrins were selected as potential carriers for obtaining, through a co-grinding technique, a stable activated amorphous form of glyburide with improved dissolution properties. Differential scanning calorimetry (DSC) was used to investigate solid-state modifications of the drug induced by co-grinding with the selected carriers in a high energy vibrational micro-mill. X-ray powder diffraction and FTIR spectroscopy were employed as additional techniques to support DSC data. Equimolar drug : cyclodextrin physical mixtures were co-ground for different times (up to 60 min) at constant vibration frequency (24 Hz). A progressive drug amorphization with increasing grinding time was observed in all binary systems, but, interestingly, different degrees of sensitivity to the mechanical-chemical activation were evident. In fact, blends with natural cyclodextrins, despite the initial higher crystallinity than those with the amorphous derivatives, required the same or shorter co-grinding times (60 min) to achieve complete drug amorphization. Stability studies indicated no appreciable drug recrystallization in co-ground products after 4 months storage in sealed containers at 25°C or 1 month at 25°C and 75% RH. No stability differences were detected between products with natural or derivative cyclodextrins. The results accounted for the suitability of cyclodextrin co-grinding technique to obtain and stabilize glyburide in the activated amorphous form. This revised version was published online in July 2006 with corrections to the Cover Date.     

Quantitative determination of metformin,glyburide and its metabolites in plasma and urine of pregnant patients by LC‐MS/MS

This report describes the development and validation of an LC‐MS/MS method for the quantitative determination of glyburide (GLB), its five metabolites (M1, M2a, M2b, M3 and M4) and metformin (MET) in plasma and urine of pregnant patients under treatment with a combination of the two medications. The extraction recovery of the analytes from plasma samples was 87–99%, and that from urine samples was 85–95%. The differences in retention times among the analytes and the wide range of the concentrations of the medications and their metabolites in plasma and urine patient samples required the development of three LC methods. The lower limit of quantitation (LLOQ) of the analytes in plasma samples was as follows: GLB, 1.02 ng/mL; its five metabolites, 0.100–0.113 ng/mL; and MET, 4.95 ng/mL. The LLOQ in urine samples was 0.0594 ng/mL for GLB, 0.984–1.02 ng/mL for its five metabolites and 30.0 µg/mL for MET. The relative deviation of this method was <14% for intra‐day and inter‐day assays in plasma and urine samples, and the accuracy was 86–114% in plasma, and 94–105% in urine. The method described in this report was successfully utilized for determining the concentrations of the two medications in patient plasma and urine. Copyright © 2014 John Wiley & Sons, Ltd.     

A Low-Resolution Separation of C14 -Glyburide and Its Metabolites from Plasma Extracts Using a High-Performance Liquid Chromatograph Guard Column

Abstract

A low-resolution method for simultaneous, rapid determination of radiolabeled glyburide and its metabolites in human plasma is described. Plasma samples were extracted with ethyl acetate. Extracts were redissolved in 300 μl of mobile phase, and injected into a 3 cm guard column, which was incorporated as a loop in a six-port switching valve. C¹⁴-glyburide was collected as a single 4-min fraction at a flow rate of 4 ml per min.

Following collection of a 1-ml fraction, the column was backflushed with methanol to allow collection of the metabolites of glyburide. The mean value of recovered radioactivity was 95.5 ± 5.7%. The validity of the separation was verified in a high-resolution HPLC system and no cross contamination of the fractions was observed.     

Simultaneous Determination of Metformin and Glyburide in Tablets by HPTLC

Simultaneous determination of two antidiabetic drugs, metformin and glyburide, in pharmaceutical tablet formulations were investigated. Normal phase thin layer chromatography plate (silica gel 60 F₂₅₄) was used as stationary phase and water/methanol/ammonium sulfate (2/1/0.5 w/v) as mobile phase to determine two pharmaceutically active ingredients, in three different formulations of Glucovance^®. This system gave a good resolution for metformin (R _f value of 0.43 ± 0.01) and glyburide (R _f value of 0.64 ± 0.02). Determination was by densitometry in the absorbance mode at 237 nm. The linear regression data for the calibration plot showed a good relationship with r = 0.99581 and 0.99982 for metformin and glyburide, respectively. The method was validated for precision and recovery. The limits of detection and quantification were 25.24 and 84.12 ng spot^?1 for metformin and 12.26 and 40.86 ng spot^?1 for glyburide, respectively. Stability study has been carried out for samples and standard solutions.