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1.
Article in English | MEDLINE | ID: mdl-33471573

ABSTRACT

As environment emerging contaminants of anthropogenic origin, antidiabetic drugs are present in the range of high ng/L to ng/mL in the influent and the effluent of the waste water treatment plant (WWTP). The metformin compound is the most used hypoglycemic agent in the world. The aim of this study was to develop a new analytic method, based on solid phase extraction followed by liquid chromatography coupled with mass spectrometric detector (SPE-LC-MS/MS), for identification and quantification of 5 antidiabetic compounds (glibenclamide/glyburide, glimepiride, metformin, glipizide, guanyl urea, gliclazide) and one degradation product (guanyl urea). The investigated environmental samples were the influent and the effluent of four urbans WWTP's. By validating of the analytical method, it was obtained low LOQ's (0.2-4.5 ng/L), satisfactory recovery rates (53.6-116.8%), and corresponding performance parameters: inter-day precision (4.9-8.4%) and reproducibility (11.3-14.6%). The concentrations of antidiabetics were as follow in influent and effluent: metformin 76-2041ng/L and 2-206ng/L, gliclazide (14.1-42.4 ng/L, and 3.3-19.1), glipizide (7.5-11.2 ng/L and 6.5-10ng/L), guanyl urea (6.2-7.3 and 8.3-21.3 ng/L). The efficiency of elimination of the antidiabetics in WWTP's was maximum for metformin (67.6-98.5%), followed, by gliclazide (72.9-78.2%). The lowest elimination efficiency was calculated for glipizide (10.7-13.3%). The guanyl urea undergoes a formation process (74.5-84.2%) in effluent, from the metformin contained in influent.


Subject(s)
Hypoglycemic Agents/analysis , Wastewater/analysis , Water Pollutants, Chemical/analysis , Chromatography, Liquid , Environmental Monitoring , Gliclazide/analysis , Glipizide/analysis , Glyburide/analysis , Metformin/analysis , Reproducibility of Results , Solid Phase Extraction , Sulfonylurea Compounds/analysis , Tandem Mass Spectrometry
2.
Rapid Commun Mass Spectrom ; 34 Suppl 4: e8651, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31721320

ABSTRACT

Patients with type 2 diabetes may co-ingest herbal and prescription medicines to control their blood sugar levels. Competitive binding of drug and herb may mutually affect their metabolism. This can alter the level of drug and its kinetics in the body, potentially causing toxicities or loss of efficacy. Understanding how the metabolism of sulfonylureas like glyburide and gliclazide can be affected by the presence of berberine and vice versa can provide valuable information on the possible risk of toxicities caused by co-ingestion of drugs. METHODS: Berberine and sulfonylureas (glyburide and gliclazide) were co-incubated with rat liver microsomes in the presence of a NADPH-regenerating system. The metabolites of berberine and sulfonylureas were analysed using liquid chromatography with high-resolution mass spectrometry in the positive ion mode. The role of individual isozymes in the metabolism of berberine, glyburide and gliclazide was investigated by using specific inhibitors. RESULTS: In vitro metabolism of berberine led to the formation of demethyleneberberine (B1a) and its isomer B1b through demethylenation. Berberrubine (B2a) and its isomer B2b were formed through demethylation. The isozymes CYP3A and CYP2D were found to be involved in the metabolism of berberine. In vitro metabolism of glyburide and gliclazide led to the formation of hydroxylated metabolites. The isozymes CYP3A and CYP2C were found to be involved in the metabolism of glyburide. Gliclazide was metabolised by CYP2C. In vitro co-incubation of glyburide or gliclazide with berberine showed that each drug's metabolism was compromised as they share a common isozyme. A strong negative linear correlation of glyburide or gliclazide metabolite levels and the concentration of berberine confirmed the effect of berberine on the metabolism of sulfonylureas. CONCLUSIONS: The metabolism of sulfonylureas and berberine was affected when these compounds were co-incubated with each other. This may be attributable to competitive binding of the herb and drug to the catalytic sites of the same isozymes.


Subject(s)
Berberine , Sulfonylurea Compounds , Animals , Berberine/analysis , Berberine/chemistry , Berberine/pharmacokinetics , Chromatography, Liquid , Cytochrome P-450 Enzyme System/metabolism , Female , Gliclazide/analysis , Gliclazide/chemistry , Gliclazide/metabolism , Glyburide/analysis , Glyburide/chemistry , Glyburide/metabolism , Herb-Drug Interactions , Male , Mass Spectrometry , Microsomes, Liver/metabolism , Rats , Sulfonylurea Compounds/analysis , Sulfonylurea Compounds/chemistry , Sulfonylurea Compounds/pharmacokinetics
3.
Talanta ; 204: 753-761, 2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31357362

ABSTRACT

In this work, novel ionic liquid (IL) functionalized polyacrylonitrile nanofibers mat (IL/PAN-NFsM) was firstly prepared through thiol-ene "click" reaction and evaluated for the establishment of a sensitive and high-throughput screening method. Because of its excellent pre-separation efficiency, IL/PAN-NFsM can adsorb trace-level targets from complex sample matrix within tens of seconds by performing a solid-phase extraction (SPE) process, and then served as sampling modules of direct analysis real time mass spectrometry (DART-MS) without any additional processing. This means the target analytes concentrated on IL/PAN-NFsM were directly desorbed, ionized, and detected by DART-MS. To verify the feasibility of the proposed method, three illegal added synthetic drugs (gliclazide, glimepiride, and gliquidone) were screened in six types of antidiabetic health-care tea samples. The results indicated that the sensitivity is in the level of ng g-1, while total analysis time does not exceed 1.0 min per sample. Moreover, the stability expressed as relative standard deviation (RSD) varies from 1.7% to 17.3%. We proposed a new screening mode based on the direct combination of functionalized NFsM and DART-MS, which is expected to become a universal method in food safety analysis.


Subject(s)
Food Contamination/analysis , Hypoglycemic Agents/analysis , Nanofibers/chemistry , Tea/chemistry , Acrylic Resins/chemistry , Allyl Compounds/chemistry , Gliclazide/analysis , Imidazoles/chemistry , Ionic Liquids/chemistry , Mass Spectrometry/methods , Solid Phase Extraction/instrumentation , Solid Phase Extraction/methods , Sulfonylurea Compounds/analysis
5.
Spectrochim Acta A Mol Biomol Spectrosc ; 215: 168-175, 2019 May 15.
Article in English | MEDLINE | ID: mdl-30836305

ABSTRACT

Prescription drug abuse can lead to serious medical negligence, so there is an urgent need to address its screening problem. Gliclazide is widely used as an antihypertensive drug for lowering blood sugar, but its excessive intake can cause serious harm to human body. Here we take gliclazide as an example to provide a method to realize the screening of drug abuse. Flower-like silver nanoparticles were prepared as surface enhanced Raman scattering (SERS) substrate, which can quantitatively and accurately detect the concentration of gliclazide. To understanding the enhanced activity of flower-like silver substrates, the Finite-Difference Time-Domain (FDTD) simulation model was established, and the simulation results showed that flower-like silver had high SERS substrate activity as well as enhanced hot spots at the rough particle surface and the adjacent particles. The experimental results indicated that the flower-shaped silver had an excellent Raman enhancement effect using R6G as detection molecules. When the gliclazide solutions with different concentration gradients were tested, the molecular vibrational modes were also obtained using Gaussian calculations. The rapid and accurate detection of gliclazide concentration was processed by Principal Component Analysis, which were consistent with the experiment, suggesting the importance of the combination of experiment and calculation. Finally, SERS substrate test was performed on the daily medication gliclazide tablets (II), which proved that the flower-like silver still has great Raman enhancement effect on the detection of actual samples.


Subject(s)
Spectrum Analysis, Raman/methods , Substance Abuse Detection/methods , Computer Simulation , Gliclazide/analysis , Humans , Metal Nanoparticles/chemistry , Models, Chemical , Principal Component Analysis , Silver/chemistry , Tablets , Vibration
6.
J Food Drug Anal ; 27(1): 315-322, 2019 01.
Article in English | MEDLINE | ID: mdl-30648585

ABSTRACT

An efficient and simple HPLC method has been developed and validated for the simultaneous determination of gliclazide and metformin hydrochloride in bulk and was applied on marketed metformin and gliclazide products. The mobile phase used for the chromatographic runs consisted of 20 mM ammonium formate buffer (pH 3.5) and acetonitrile (45:55, v/v) The separation was achieved on an Alltima CN (250 mm × 4.6 mm x5µ) column using isocratic mode. Drug peaks were well separated and were detected by a UV detector at 227 nm. The method was linear at the concentration range 1.25-150 µg/ml for gliclazide and 2.5-150 µg/ml for metformin respectively. The method has been validated according to ICH guidelines with respect to system suitability, specificity, precision, accuracy and robustness. Metformin limit of detection (LOD) and limit of quantification (LOQ) were 0.8 µg/ml and 2.45 µg/ml respectively while LOD and LOQ for gliclazide were 0.97 µg/ml and 2.95 µg/ml respectively.


Subject(s)
Chromatography, High Pressure Liquid/methods , Gliclazide/analysis , Hypoglycemic Agents/analysis , Metformin/analysis , Limit of Detection , Sensitivity and Specificity
7.
J AOAC Int ; 102(4): 1112-1124, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-30658719

ABSTRACT

Background: Quantitative multicomponent analysis is considered an analytical goal to save time and cost in analysis. Objective: This work aimed to provide sensitive and selective [successive ratio subtraction coupled with constant multiplication (SRS-CM) and chemometric] methods for the determination of coformulated antidiabetic drugs, namely canagliflozine and metformin or gliclazide and metformin in presence of metformin degradation product, 1-cyanoguanidine. Methods: SRS-CM method was developed for the determination of canagliflozin and metformin at 292 and 237 nm, respectively, using 14 µg/mL canagliflozin as a divisor in the first step to cancel the spectrum of canagliflozin. Then, 18 µg/mL metformin was used as a divisor in the second step to cancel the spectrum of metformin. Finally, we obtained the spectrum of cyanoguanidine. Chemometric method was applied for the determination of the gliclazide and metformin mixture in a 225-235 nm range. Sample enrichment technique was used to increase the concentration of canagliflozin or gliclazide to allow its simultaneous determination with metformin without prior separation. Results: Validation parameters according to the International Conference on Harmonization guidelines were satisfactory over the concentration ranges of 5 to 16 µg/mL for canagliflozin and metformin as well as 2.5 to 12.5 and 6 to 24 µg/mL for gliclazide and metformin, respectively. Conclusions: The method provides sufficient selectivity and accuracy to be applied for routine analysis and quality control in laboratories for the cited drugs. Highlights: This work shows two examples to how to select a suitable UV spectrophotometric method to overcome the spectral overlap.


Subject(s)
Canagliflozin/analysis , Gliclazide/analysis , Hypoglycemic Agents/analysis , Metformin/analysis , Spectrophotometry, Ultraviolet/methods , Drug Contamination , Guanidines/chemistry
8.
Ars pharm ; 59(2): 85-90, abr.-jun. 2018. graf, tab
Article in English | IBECS | ID: ibc-177724

ABSTRACT

Aim: This research is dedicated to development of a methodology for the determination of gliclazide in biological samples for analytical diagnostics of lethal overdose caused by the drug. Materials and Methods: TLC method: chromatographic plates Merck silica gel 60 F254 10×10 cm in size, mobile phase - ethyl acetate, visualization reagent 1% vanillin solution or 5% solution of chloral hydrate. HPLC method: liquid chromatograph «Milichrom-A-02» with UV detecting (RF); Prontosil-120-5-C18-AQ reverse-phase column Ø2×75 mm in diameter, 5 µm grains (Bischoff Analysetechnik und Geräte GmbH, Germany); Gradient elution with a mixture of two eluents (eluent A - [0.2 M solution LiClO4 - 0.005 M solution of HClO4] and eluent B - acetonitrile); Wavelength 230 nm. Results: Methodology for the determination of gliclazide in biological samples is developed. It includes an effective method of gliclazide isolation from the objects of the study, specific and selective chromatographic detection methods and quantitative determination of toxicity in the extracts that had been received. It was established that while using TLC method gliclazide was assigned an Rf value of 0,48 ± 0,01; detection limit is 3.0 µg. When applying HPLC method gliclazide holding time was 7.80 min (RSD = 0.13%), detection limit was 0.050 µg / ml, limit of the quantitative determination was 0.157 µg/ml, linearity of the procedure was in the range of 0.1-20.0 mig/ml. Under the developed conditions, gliclazide was determined at 17.48 ± 1.32 mig/ml (RSD = 6.06%). Conclusions: Results of the study indicate that methodology for the determination of gliclazide in biological samples that was developed can be used for analytical diagnostics of lethal overdose caused by the drug


Objetivo: Desarrollar un método de detección de gliclazida en muestras biológicas para el diagnóstico analítico de los fallecimientos por sobredosis del fármaco. Materiales y métodos: Método de CCF: placas para cromatografía Merck silica gel 60 F254 de 10×10 cm de tamaño, fase móvil - acetato de etilo, revelador - solución al 1% de vainillina o solución al 5% de hidrato de cloral. Método de HPLC: cromatógrafo líquido "Milihrom-A-02" con detección de UV (Rusia); columna de fase inversa Prontosil-120-5-C18-AQ de Ø2 x 75 mm, con graneado de 5 mm ("Bischoff Analysetechnik und Geräte GmbH», Alemania); elución gradiente con una mezcla de dos eluyentes (eluyente A - [0,2 M solución de LiClO4 - solución de HClO 0,005 M4] y eluyente B - acetonitrilo); la longitud de onda es de 230 nm. Resultados y discusión: Se desarrolló una metodología de determinación de la gliclazida en muestras biológicos, que incluye un método eficaz de aislar la gliclazida de los objetos de estudio, unos métodos cromatográficos específicos y selectivos de detección y cuantificación de la sustancia tóxica en los extractos obtenidos. Se constató que al aplicarse el método de CCF la gliclazida ha sido identificada de acuerdo con el valor Rf 0,48±0,01; el límite de detección es de 3,0 µg. Al aplicarse el método de HPLC se constató lo siguiente: el tiempo de retención de la gliclazida es de 7,80 min (RSD=0,13%), el límite de detección es de 0,050 µg/ml, el límite de cuantificación es de 0,157 µg/ml, la linealidad del método está en el intervalo de 0,1-20,0 µg/ml. En condiciones diseñadas la gliclazida se detectó a un nivel de 17,48±1,32µg/ml (RSD=6,06%). Conclusiones. Los resultados obtenidos confirman que la metodología desarrollada de detección de la gliclazida en muestras biológicos es adecuada para el diagnóstico analítico de los fallecimientos por sobredosis del fármaco


Subject(s)
Humans , Gliclazide/analysis , Gliclazide/pharmacology , Biological Specimen Banks , Drug Overdose/diagnosis , Drug Overdose/mortality , Chromatography, Liquid/methods , Laboratory and Fieldwork Analytical Methods/methods
9.
Eur J Pharm Biopharm ; 119: 56-67, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28583588

ABSTRACT

The formation of molecularly dispersed amorphous solid dispersions by the hot-melt extrusion technique relies on the thermal and mechanical energy inputs, which can cause chemical degradation of drugs and polymeric carriers. Additionally, drug degradation may be exacerbated as drugs convert from a more stable crystalline form to a higher energy amorphous form. Therefore, it is imperative to study how drug degrades and evaluate methods to minimize drug degradation during the extrusion process. In this work, gliclazide was used as a model thermally labile drug for the degradation kinetics and process optimization studies. Preformulation studies were conducted using thermal analyses, and liquid chromatography-mass spectroscopy to identify drug degradation pathways and to determine initial extrusion conditions. Formulations containing 10% drug and 90% AFFINISOL™ HPMC HME 100LV were then extruded using a twin screw extruder, and the extrudates were characterized using X-ray powder diffraction, modulated dynamic scanning calorimetry, and potency testing to evaluate physicochemical properties. The energies of activation for both amorphous gliclazide, crystalline gliclazide, and gliclazide solution were calculated using the Arrhenius equation to further guide the extrusion optimization process. Preformulation studies identify two hydrolysis degradation pathways of gliclazide at elevated temperatures. The activation energy study indicates a significantly higher degradation rate for the amorphous gliclazide compared to the crystalline form. After optimization of the hot-melt extrusion process, including improved screw designs, machine setup, and processing conditions, gliclazide amorphous solid dispersion with ∼95% drug recovery was achieved. The ability to process thermally labile drugs and polymers using hot-melt extrusion will significantly expand the possible applications of this manufacturing process.


Subject(s)
Chemistry, Pharmaceutical/methods , Gliclazide/analysis , Gliclazide/chemical synthesis , Hot Temperature , Calorimetry, Differential Scanning/methods , Thermogravimetry/methods , X-Ray Diffraction/methods
10.
AAPS PharmSciTech ; 18(5): 1785-1794, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27800567

ABSTRACT

In the absence of an official dissolution method for modified-release tablets of gliclazide, dissolution parameters, such as apparatuses (1, 2, and 3), rotation speeds, pH, and composition of the dissolution medium were investigated. The results show that although the drug presents a pH-mediated solubility (pH 7.0 > 6.8 > 6.4 > 6.0 > 5.5 > 4.5), the in vitro release of the studied tablets was not dependent on this parameter, despite of the apparatus tested. On the other hand, the rotation speed demonstrated a greater influence (100 rpm >50 rpm). Using similar hydrodynamic conditions, the three different apparatuses were compared in pH 6.8 and provided the following trend: apparatus 1 at 100 rpm >2 at 50 rpm ≈3 at 10 dpm. As a complete, but slow release is expected from modified-release formulations, apparatus 2, in phosphate buffer pH 6.8 and 100 rpm, were selected as the optimized dissolution method. In comparison to apparatus 1 under the same conditions, the paddle avoids the stickiness of formulation excipients at the mesh of the basket, which could prejudice the release of gliclazide. Results obtained with biorelevant medium through the developed dissolution method were similar to the buffer solution pH 6.8. The application of the optimized method as a quality control test between two different brands of gliclazide modified-release tablets showed that both dissolution profiles were considered similar by the similarity factor (f2 = 51.8). The investigation of these dissolution profiles indicated a dissolution kinetic following first-order model.


Subject(s)
Chemistry, Pharmaceutical/methods , Gliclazide/analysis , Gliclazide/chemistry , Delayed-Action Preparations/analysis , Delayed-Action Preparations/chemistry , Excipients/analysis , Excipients/chemistry , Solubility , Tablets/chemistry
11.
J Chromatogr A ; 1416: 112-20, 2015 Oct 16.
Article in English | MEDLINE | ID: mdl-26381571

ABSTRACT

A method combining on-line immunoextraction microcolumns with high-performance affinity chromatography (HPAC) was developed and tested for use in examining drug-protein interactions with normal or modified proteins. Normal human serum albumin (HSA) and glycated HSA were used as model proteins for this work. High-performance immunoextraction microcolumns with sizes of 1.0-2.0 cm × 2.1mm i.d. and containing anti-HSA polyclonal antibodies were developed and tested for their ability to bind normal HSA or glycated HSA. These microcolumns were able to extract up to 82-93% for either type of protein at 0.05-0.10 mL/min and had a binding capacity of 0.34-0.42 nmol HSA for a 1.0 cm × 2.1mm i.d. microcolumn. The immunoextraction microcolumns and their adsorbed proteins were tested for use in various approaches for drug binding studies. Frontal analysis was used with the adsorbed HSA/glycated HSA to measure the overall affinities of these proteins for the drugs warfarin and gliclazide, giving comparable values to those obtained previously using similar protein preparations that had been covalently immobilized within HPAC columns. Zonal elution competition studies with gliclazide were next performed to examine the specific interactions of this drug at Sudlow sites I and II of the adsorbed proteins. These results were also comparable to those noted in prior work with covalently immobilized samples of normal HSA or glycated HSA. These experiments indicated that drug-protein binding studies can be carried out by using on-line immunoextraction microcolumns with HPAC. The same method could be used in the future with clinical samples and other drugs or proteins of interest in pharmaceutical studies or biomedical research.


Subject(s)
Chromatography, Affinity/methods , Drug Interactions , Gliclazide/analysis , Serum Albumin/analysis , Warfarin/analysis , Anticoagulants/analysis , Anticoagulants/chemistry , Anticoagulants/metabolism , Gliclazide/chemistry , Gliclazide/metabolism , Glycosylation , Humans , Hypoglycemic Agents/analysis , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/metabolism , Protein Binding , Serum Albumin/chemistry , Serum Albumin/metabolism , Warfarin/chemistry , Warfarin/metabolism
12.
J Chromatogr Sci ; 53(6): 993-9, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25344839

ABSTRACT

A fast capillary zone electrophoretic method with photodiode array detection (CZE-PAD) was established and validated for assays of commonly prescribed anti-diabetic drugs [metformin (MET), glibenclamide (GBM) and gliclazide (GCZ)] in 13 samples including raw material, single and combined tablets. CZE optimization revealed baseline separation of the analytes (Rs > 5.39) in 8 min, in 50 mM borate buffer (pH 9.0), using a capillary with an effective length of 56.0 cm and an inner diameter of 50 µm, a voltage of 20 kV, a temperature of 25°C and a detection wavelength at 210 nm. The method provides excellent linearity, precision (%RSDs < 1.90%), recovery (99.8-101.0%) and low detection and quantitation limits (<4 and 12 µg/mL, respectively). The procedure was fast (seven samples per hour) and cost effective, since no organic solvent, sample pre-treatments or clean-up procedures were required. Importantly, the method was accurate, sensitive and reliable for routine quality control of MET, GBM and GCZ in pharmaceutical products both in single and combined formulations.


Subject(s)
Gliclazide/analysis , Glyburide/analysis , Hypoglycemic Agents/analysis , Metformin/analysis , Drug Combinations , Electrophoresis, Capillary/methods , Gliclazide/chemistry , Glyburide/chemistry , Hypoglycemic Agents/chemistry , Limit of Detection , Linear Models , Metformin/chemistry , Reproducibility of Results , Tablets
13.
J Pharm Biomed Anal ; 102: 119-28, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25260054

ABSTRACT

A stability indicating-micellar electrokinetic chromatography method was developed and validated for the determination of gliclazide (GCZ) and its specified impurities, gliclazide impurities B (GZB) and F (GZF) in bulk and tablets. The analytes were well separated (Rs>2.1) in 5 min using 10mM phosphate buffer (pH 7.0) containing 15 mM sodium dodecyl sulfate on a fused-silica capillary with an effective length of 40 cm and an inner diameter of 50 µm, injection at 50 mbar for 5s, temperature of 25°C, applied voltage of 20 kV and photodiode array detection at 225 nm. The method showed good linearity (r(2)>0.99, in the ranges of 128-192, 20-60 and 10-50 µg/mL for GCZ, GZB and GZF, respectively) and precision (%RSD for intra- and inter-day precision of less than 2.00%, n=3) for all compounds. Accuracy represented as %recovery was between 99.1 and 100.1% with %RSDs of less than 0.59% (n=3). Limits of detection and quantitation were less than 40 and 120 µg/mL, respectively. The method was robust with %RSDs of migration time and peak areas of less than 1.36% (n=9), when buffer and separating voltage were altered around the optimal values. Stress tests showed that GCZ was stable in alkaline hydrolysis both at room and elevated temperature. However, GCZ degraded under acid and neutral hydrolysis and oxidation condition. Elevated temperature and exposure to sunlight accelerated GCZ degradation and formation of GZB and an unknown degradation product. Stability profiles and degradation kinetics of GCZ could be established using the MEKC method. In addition, the method could be used for assay of GCZ in raw material and commercial tablets and results revealed that contents of GCZ in all samples were within the pharmacopeia limit. No degradation products, especially GZB and GZF, were observed in the investigated samples.


Subject(s)
Drug Stability , Gliclazide/analogs & derivatives , Gliclazide/analysis , Chromatography, Micellar Electrokinetic Capillary , Powders/analysis , Tablets/analysis
14.
Chem Commun (Camb) ; 50(97): 15397-9, 2014 Dec 18.
Article in English | MEDLINE | ID: mdl-25349979

ABSTRACT

A lithium-rich composite metal oxide was evaluated as a novel matrix for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-MS). The low background interference and lithium-rich feature made it a highly efficient matrix for the analysis of small molecules with high reproducibility, sensitivity and strong salt tolerance.


Subject(s)
Lithium/chemistry , Oxides/chemistry , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Chelating Agents/chemistry , Citric Acid/chemistry , Cyclodextrins/analysis , Cyclodextrins/chemistry , Edetic Acid/chemistry , Gliclazide/analysis , Gliclazide/chemistry , Glipizide/analysis , Glipizide/chemistry , Lipids/analysis , Lipids/chemistry , Oligosaccharides/analysis , Oligosaccharides/chemistry , Peptides/analysis , Peptides/chemistry
15.
Forensic Sci Int ; 223(1-3): 119-24, 2012 Nov 30.
Article in English | MEDLINE | ID: mdl-22940189

ABSTRACT

A sensitive and accurate LC-MS/MS method for the identification and quantification of 5 oral anti-diabetics (glipizide, glibenclamide, gliclazide, gliquidone and metformin) in serum and hair was developed using glibornuride as the internal standard. We have developed a rapid and robust extraction procedure by using acetonitrile for serum protein precipitation and methanol for the extraction of anti-diabetics from hair. Anti-diabetics (ADs) were separated by UPLC over a C18 column and detection was performed on a Waters Xevo TQ MS mass spectrometer in positive ionization mode using electrospray ionization. Each AD was identified by three specific ion transitions in multiple reaction monitoring (MRM) mode. The method was validated according to international guidelines. For all compounds the variation coefficient (CV) was <20%, and accuracies ranged from 85 to 115% in serum and hair. The limits of detection (LODs) were <1.5 ng/mL for all ADs in serum and <3.59 pg/mg in hair. Recoveries varied from 56.41% (gliclazide) to 67.58% (glipizide) in serum and from 68% (gliclazide) to 91.2% (metformin) in hair. The method was successfully applied to quantify ADs in serum of 33 patients and in hair of 15 patients.


Subject(s)
Chromatography, Liquid , Hair/chemistry , Hypoglycemic Agents/analysis , Mass Spectrometry , Acetonitriles , Female , Forensic Toxicology/methods , Gliclazide/analysis , Gliclazide/chemistry , Glipizide/analysis , Glipizide/chemistry , Glyburide/analysis , Glyburide/chemistry , Humans , Hypoglycemic Agents/chemistry , Limit of Detection , Male , Metformin/analysis , Metformin/chemistry , Methanol , Middle Aged , Molecular Structure , Solvents , Sulfonylurea Compounds/analysis , Sulfonylurea Compounds/chemistry
16.
Anal Bioanal Chem ; 401(9): 2811-9, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21922305

ABSTRACT

This study used high-performance affinity chromatography (HPAC) to examine the binding of gliclazide (i.e., a sulfonylurea drug used to treat diabetes) with the protein human serum albumin (HSA) at various stages of modification due to glycation. Frontal analysis conducted with small HPAC columns was first used to estimate the number of binding sites and association equilibrium constants (K(a)) for gliclazide with normal HSA and glycated HSA. Both normal and glycated HSA interacted with gliclazide according to a two-site model, with a class of high-affinity sites (average K(a), 7.1-10 × 10(4) M(-1)) and a group of lower-affinity sites (average K(a), 5.7-8.9 × 10(3) M(-1)) at pH 7.4 and 37 °C. Competition experiments indicated that Sudlow sites I and II of HSA were both involved in these interactions, with the K(a) values for gliclazide at these sites being 1.9 × 10(4) and 6.0 × 10(4) M(-1), respectively, for normal HSA. Two samples of glycated HSA had similar affinities to normal HSA for gliclazide at Sudlow site I, but one sample had a 1.9-fold increase in affinity at this site. All three glycated HSA samples differed from normal HSA in their affinity for gliclazide at Sudlow site II. This work illustrated how HPAC can be used to examine both the overall binding of a drug with normal or modified proteins and the site-specific changes that can occur in these interactions as a result of protein modification.


Subject(s)
Carrier Proteins/analysis , Chromatography, Affinity/methods , Gliclazide/analysis , Hypoglycemic Agents/analysis , Serum Albumin/analysis , Binding Sites , Binding, Competitive , Calibration , Carrier Proteins/chemistry , Carrier Proteins/metabolism , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Gliclazide/chemistry , Gliclazide/metabolism , Gliclazide/pharmacology , Glycosylation , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/metabolism , Hypoglycemic Agents/pharmacology , Kinetics , Protein Binding , Sensitivity and Specificity , Serum Albumin/chemistry , Serum Albumin/metabolism
17.
Braz. j. pharm. sci ; 47(1): 161-166, Jan.-Mar. 2011. graf
Article in English | LILACS | ID: lil-586536

ABSTRACT

The present study was initiated with the objective of studying the in vitro dissolution behavior of gliclazide from its solid dispersion with polyethylene glycol 6000. In this work, a solid dispersion of gliclazide with polyethylene glycol was prepared by the fusion method. In vitro dissolution study of gliclazide, its physical mixture and solid dispersion were carried out to demonstrate the effect of PEG 6000. Analytical techniques of FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry were used to characterize the drug in the physical mixtures and solid dispersions. The dissolution studies of solid dispersion and physical mixture showed greater improvement compared to that of the pure drug. The mechanisms for increased dissolution rate may include reduction of crystallite size, a solubilization effect of the carrier, absence of aggregation of drug crystallites, improved wettability and dispersbility of the drug from the dispersion, dissolution of the drug in the hydrophilic carrier or conversion of drug to an amorphous state. The FT-IR spectra suggested that there was no interaction between gliclazide and PEG 6000 when prepared as a solid dispersion. DSC and XRD study indicated that the drug was converted in the amorphous form.


O presente trabalho foi realizado com o objetivo de estudar o comportamento in vitro da dissolução da gliclazida a partir da sua dispersão sólida com polietileno glicol 6000. Neste trabalho, as dispersões sólidas de gliclazida com polietileno glicol foram preparadas pelo método de fusão. Os estudo de dissolução in vitro da gliclazida, na mistura física e nas dispersões sólidas foram realizados para demonstrar o efeito de PEG 6000. Técnicas analíticas como espectroscopia FT-IR, calorimetria diferencial de varredura e difração de raios-X foram empregadas para caracterizar o fármaco nas misturas físicas e nas dispersoes sólidas. Os estudos de dissolução demonstraram maior melhoria. Os mecanismos para aumentar a velocidade de dissolução podem incluir a redução do tamanho dos cristais, a solubilização do carreador, a ausência de agregação dos cristais do fármaco, a melhoria da molhabilidade e dispersibilidade do fármaco a partir da dispersão, a dissolução do fármaco no carreador hidrofílico ou conversão da forma cristalina do fármaco para estado amorfo. Os espectros de FT-IR sugeriram que não houve interação entre gliclazide PEG 6000 e na sua combinação. Os estudos de DSC e DRX indicaram que o fármaco foi convertido para a forma amorfa.


Subject(s)
Drug Evaluation , Dissolution/statistics & numerical data , Gliclazide/analysis , In Vitro Techniques , Propylene Glycol/pharmacology , Drug Compounding
18.
Arch. venez. farmacol. ter ; 30(2): 28-32, 2011. tab, graf
Article in Spanish | LILACS | ID: lil-699596

ABSTRACT

El objetivo principal consistió en conocer la biodisponibilidad relativa de una nueva formulación de gliclazida (Gliclazida comprimidos de liberación sostenida Laboratorios Genven) con respecto a la formulación de Laboratorios Servier tomada como referencia, y establecer su bioequivalencia de acuerdo a los criterios recomendados por las autoridades sanitarias. Se hizo asimismo una valoración de la tolerancia de ambos preparados. Se diseñó un estudio abierto, randomizado, cruzado, dos periodos, con siete días de lavado, con 12 voluntarios sanos de ambos sexos, entre 21 y 55 años, quienes ingirieron un comprimido del fármaco en estudio: GLICLAZIDA comprimidos DE LIBERACIÓN SOSTENIDA de 30 mg, fabricados por Laboratorios GENVEN, o del Fármaco control: GLICLAZIDA comprimidos DE LIBERACIÓN SOSTENIDA de 30 mg, fabricados por Laboratorios SERVIER, comercializados en Venezuela con el nombre de DIAMICROM MR®. La bioequivalencia se determinó con los parámetros farmacocinéticos de área bajo la curva AUC (0-t), AUC 0-∞ y concentración máxima (Cmax). Con ambas formulaciones se inicia la aparición en plasma de niveles cuantificables desde los 30 minutos, ambos productos alcanzan su Cmax alrededor de las 12 horas, con una Cmax para Gliclazida de Laboratorios Genven (GL) de 558.57 +/- 191.43 ng/mL y para Gliclazida marca Diamicrón MR® (GD) de 514.56 +/- 140.94 ng/mL sin diferencias significativas (P= 0.66). En cuanto al área debajo de la curva (AUC), encontramos valores de AUC 0-t de 539.68 +/- 210.75 ng/mL/h para GL y de 585.07 +/- 240.66 ng/mL/h para GD sin diferencias significativasentre estas (P= 0.91). Para el AUC0-∞ los valores fueron de 569.14 +/- 216,95 ng/mL/h para GL y de 616.93 +/- 244.37ng/mL/h para GD (P= 0.71)


The main objective was evaluated the relative bioavailability of a new formulation of gliclazide (gliclazide sustained release tablets Genven Laboratories) regarding the formulation of Laboratoires Servier taken as a reference and establish their bioequivalence according to the criteria recommended by health authorities. It was also an assessment of tolerance of both preparations. We performed a study open, randomized, crossover two periods, with seven days of washing, with 12 healthy volunteers of both sexes, between 21 and 55 years who ate a pill in drug study: GLICLAZIDE Liberation sustainable tablets 30 mg, manufactured by Genven Laboratories or drug control: GLICLAZIDE Liberation sustainable tablets 30 mg, manufactured by Servier Laboratories in Venezuela, marketed under the name DIAMICROM MR®. The bioequivalence was determined with the pharmacokinetic parameters of area under the curve AUC (0-t), AUC 0-∞ and maximum concentration (Cmax). With both formulations began appearing on plasma levels quantifiable from the 30 minutes, both product’s reach their Cmax around 12 hours, with a Cmax for gliclazide Genven Laboratory (GL) from 558.57 +/- 191.43 ng/mL and Gliclazide Diamicron MR® (GD) from 514.56+/-140.94 ng/mL without significant differences (P= 0.66). As for the area under the curve (AUC) values were found AUC 0-t 539.68 +/-210.75 ng/mL/h for GL and 585.07 +/- 240.66 ng/mL/h for GD no significant differences between these (P= 0.91). For AUC 0-∞ values were 569.14 +/- 216.95 ng/mL/h for GL and 616.93 +/- 244.37 ng/mL/h for GD (P= 0.71)


Subject(s)
Middle Aged , Biological Availability , Gliclazide/analysis , Gliclazide/adverse effects , Pharmacokinetics , Pharmaceutical Preparations/analysis , Therapeutic Equivalency , Pharmacology
19.
Drug Dev Ind Pharm ; 36(8): 893-902, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20196643

ABSTRACT

BACKGROUND: This study investigated the physical interaction of gliclazide (GLC) with a hydrophilic carrier, that is, macrogol [polyethylene glycol (PEG)]. Different molecular weights of PEG (4000, 10,000, and 20,000) were used in different drug : carrier weight ratios (1 : 1, 1 : 2, 1 : 5, and 1 : 10). METHOD: Preliminary screening was done by phase solubility studies to characterize the liquid state interaction between the drug and the carrier. Solid dispersions (SDs) of GLC and PEG in different ratios were prepared by fusion technique and by physical mixing. The solid-state interaction between the drug and the carrier was examined by performing differential scanning calorimetry and Fourier transform infrared spectroscopic studies. SD with satisfactory characteristics was selected for the formulation of tablets by wet granulation method and compared with the commercial brand for in vitro dissolution. RESULTS: It was evident from phase solubility studies that the drug solubility increased linearly with increasing PEG concentrations. In vitro dissolution of GLC improved significantly in the SDs prepared by fusion method as compared with the original drug and physical mixtures. Scanning electron microscopy images showed well-defined changes in the surface topography of GLC, thus confirming the effective formation of a fused binary system. The SD tablets showed a significant improvement in the drug release profile than that of the commercial brand. CONCLUSION: It was thus concluded that SD formulations of GLC can be successfully used to design a solid dosage form of the drug, which would have significant advantages over the current marketed tablets.


Subject(s)
Drug Carriers/chemistry , Gliclazide/administration & dosage , Gliclazide/chemistry , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/chemistry , Polyethylene Glycols/chemistry , Calorimetry, Differential Scanning , Chemical Phenomena , Drug Carriers/administration & dosage , Drug Carriers/analysis , Drug Compounding , Gliclazide/analysis , Hydrophobic and Hydrophilic Interactions , Hypoglycemic Agents/analysis , Kinetics , Molecular Weight , Osmolar Concentration , Solubility , Spectroscopy, Fourier Transform Infrared , Surface Properties , Suspensions , Tablets
20.
J Pharm Biomed Anal ; 51(4): 973-8, 2010 Mar 11.
Article in English | MEDLINE | ID: mdl-20004074

ABSTRACT

Recently, charged aerosol detection (CAD), a new kind of universal detection method, has been widely employed in the HPLC system. In the present study, four kinds of anti-diabetic drug standards, glipizide, gliclazide, glibenclamide and glimepiride were determined by ultraviolet (UV) detection, evaporative light scattering detection (ELSD) and the aforementioned CAD. The results were compared with reference to linearity, accuracy, precision and limit of detection (LOD). All of the experiments were performed on a reverse phase column with water and acetonitrile as the mobile phase. Separations were achieved under the same chromatographic conditions for each detection method. As a result, CAD generated nearly uniform responses compared with UV detection and ELSD. It showed the best accuracy and LOD among 3 detectors and had similar precision with UV detection at higher concentrations while UV detection showed a better precision at lower concentrations than did CAD or ELSD. The LOD of CAD, in fact, can be up to two times higher than that of ELSD. The UV and ELSD linearity was satisfactory at R(2)>0.99, though in the case of CAD, a log-log transformation was needed. The proposed methods were also applied to the real anti-diabetic drugs and diabetes-related dietary supplements.


Subject(s)
Chromatography, High Pressure Liquid , Chromatography, Reverse-Phase , Hypoglycemic Agents/analysis , Light , Scattering, Radiation , Spectrophotometry, Ultraviolet , Aerosols , Gliclazide/analysis , Glipizide/analysis , Glyburide/analysis , Reproducibility of Results , Sulfonylurea Compounds/analysis
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