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Analysis of glimepiride by using derivative UV spectrophotometric method

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Abstract

Glimepiride (Amaryl), which is a new oral antidiabetic drug in the sulfonylurea class, was analysed by using second order derivative UV spectrophotometry. The quantification of glimepiride in dimethylformamide was performed in the wavelength range of 245-290 nm at N = 6, ?lambda = 21. The second order derivative spectra was calculated using peak to peak (lambdaDMF = 263.3-268.2 nm), peak to zero (lambdaDMF = 268.2 nm) and tangent (lambdaDMF = 263.3-271.8 nm) method for calibration curves, the linearity range of 1.00-500.00 microg ml(-1) by using the second order derivative UV spectrophotometric method. The developed method was applied to directly and easily to the analysis of the pharmaceutical tablet preparations. R.S.D. were found to be 4.18% (Amaryl tablet; 1 mg) and 2.21% (Amaryl tablet; 2 mg). The method was completely validated and proven to be rugged. The limit of quantitation and the limit of detection were found as 1.00 and 0.4 microg ml(-1), respectively. This validated derivative UV spectrophotometric method is potentially useful for a routine laboratory because of its simplicity, rapidity, sensitivity, precision and accuracy.

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... Simple and fast simultaneous estimation of drug concentrations in their mixture or therapeutic delivery systems is posing a real challenge to formulators. Recently , many estimation techniques were developed on raw overlapping spectral data to enable mixture resolution, such as different order derivatives [7][8][9] , derivatives of the ratio spec- trum [10,11] and ratio subtraction technique [12]. Valuable researches were published based on using simultaneous equation (Vierordt's method) for estimation of 2 or more drugs in combined mixtures or pharmaceutical dosage forms [13][14][15][16]. ...
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For sake of improving patient compliance and sustainability of chemotherapy healthcare system, both TC and CoQ10 were formulated as solid lipid nanoparticles (SLNs). The study was focused on establishing and validation of a simple and reproducible spectrophotometric method for simultaneous determination of TC and CoQ10 in their binary mixture or pharmaceutical dosage forms. A new method based on simultaneous estimation of drugs mixture without prior separation was developed. Validation parameters were checked with International Conference on Harmonization (ICH) guidelines. The accuracy and reproducibility of proposed method was statistically compared to HPLC. The TC and CoQ10 were quantified at absorptivity wavelengths of 236nm and 275nm, respectively. Calibration curves obeyed Beer's law in range of 2-14µg/ml with a correlation coefficient (R2) of 0.999 in both methanol and simplified simulated intestinal fluid (SSIF). The %means recovery of TC and CoQ10 in pure state or binary mixture at various concentration levels were all around 100%. The low values of SD and %RSD (<2%) confirm high precision and accuracy of the proposed method. Formulated SLNs showed different %means recovery in range 81-92% for TC and 32-59% for CoQ10. The data obtained by applying simultaneous Vierordt's equations showed no statistical significance in comparison to HPLC. Vierordt's method was successfully applied as simple, accurate, precise, and economical analysis method for estimating TC and CoQ10 concentrations in pure state, binary mixture and pharmaceutical dosage forms.
... Several methods have been reported for determination of Glimepiride either alone or in combined dosage forms. The methods include spectrophotometric [28][29][30][31][32][33][34][35], HPLC [22][23][24] and [36][37] and HPTLC [38,39]. then diluted to the mark with the mobile phase. ...
... The developed method was applied to determine the valsartan and glimepiride in pharmaceutical formulations. The results obtained were compared with UV-spectrophotometric method given in the literature (Altinoz and Tekeli, 2001). ...
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In this work an electrochemical quantification and interaction of valsartan and glimepiride were studied on hanging mercury drop electrode (HMDE) using square wave voltammetric (SWV) technique. The effect of temperature on the interaction was investigated in eight degrees of heat and the thermodynamics parameters (enthalpy, entropy & free gibbs energy) were calculated for the interaction using Van't Hoff equation and binding constant (K) also obtained from interaction equation. From the values of the calculated thermodynamic parameters it found that the main bonding forces that predominated over the interaction were Vander Waals and Hydrogen bonding. The calibration curves of each drug was liner with R 2 value equal to 0.9819, 0.997 and the limit of detection was found to be 4.99 x 10-7 , 3.48 x 10-8 for valsartan and glimepiride respectively. Through the limit of detection, this method can be used as a standard method in estimating the pharmacists in pharmaceutics and verifying the credibility of the manufacturers of the two drugs.
... Several manipulations were performed on the raw overlapping spectral data to enable mixture resolution, for example, using different order derivatives [1] [2] [3] [4] [5] [6], derivatives of the ratio spectrum [7] [8] [9] [10] and ratio subtraction technique [11]. ...
Article
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A new simple spectrophotometric method was developed for the simultaneous determination of drugs with interfering spectra in binary mixtures without previous separation. The new method is based on a simple modification for the ratio subtraction method. This modification enabled wider range of application. The proposed ratio difference method was applied for the determination of brimonidine and timolol in laboratory prepared mixtures with mean percentage recoveries 100.40±2.29 and 101.23±1.30 respectively, and in their pharmaceutical formulation with mean percentage recoveries 101.08±0.44 and 100.66±0.52 respectively. The suggested ratio difference method was validated according to USP guidelines and can be applied for routine quality control testing.
... As a result of the importance of this oral hypoglycaemic agent in the treatment of noninsulin-dependent diabetes mellitus DM, this work aims to compile the published analytical methods reported so far in the literature for determination of degraded products of glimepiride in biologic samples and pharmaceutical formulations [6]- [10]. Techniques like high-performance liquid chromatography with ultraviolet, mass spectroscopy, arraydiode, evaporative light scattering and liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry, ionization-tandem mass spectrometry, high-performance liquid chromatography with columnswitching, micelle electro kinetic chromatography, high-performance thin layer chromatography, and spectrophotometry have been used for analysis, from which we have seen that high-performance liquid chromatography methods have been used most extensively [11] [12]. The aim of present work is to develop and validate a simple UV spectrophotometric method to be applied for analysis of glimepiride degradation in tablets, which serves as a tool for the quality control of pharmaceutical dosage forms. ...
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The objective of this study is to develop the degradation studies of different brands of glimepiride available in market. Forced degradation is a powerful tool used routinely in pharmaceutical development in order to develop stability-indicating methods that lead to quality stability data and to understand the degradation pathways of the drug substances and drugs. Glimepiride is a medium-to long-acting sulfonylurea antidiabetic drug as it is the most prescribed oral antihyper glycaemic agent indicated to treat type 2 diabetes mellitus. Its mode of action is to increase insulin production by the pancreas. This is not used for type 1 diabetes because in type 1 diabetes the pancreas is not able to produce insulin. Glimepiride was subjected to different stress conditions as per (ICH) International Conference on Harmonization guidelines. Distilled water was used as solvents and the amount of drug was calculated after degradation by taking absorbance at 200 nm. According to the assay limit of USP specified that the content should not be less than 95% and not more than 105% of labelled amount. On basic pH brand A, and E showed degradation after the addition of 0.1 N base while other brands degraded as base has no impact on glimepiride concentration. On addition of 0.1 N HCl only brand E showed heavy degradation. After 48 hours the absorbance of all brands are different compared with initial absorbance which shows degradation of all brands.
... HPLC analysis of atorvastatin along with two drugs (ramipril and aspirin) has also been reported 7 . Similarly, a survey of the analytical literature for glimepiride revealed that methods based on UV Spectrophotometry and HPLC are available for determination of glimepiride in pharmaceuticals either single or combine with other drugs [8][9][10][11] . ...
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A simple, precise, accurate and reproducible spectrophotometric method has been developed and validated for the quantification of atorvastatin and glimepiride in tablet dosage form by simultaneous equation method. Two spectrophotometers (Shimadzu, UV-1700 & UV-1601) were used for validation and absorbances were recorded at 241 nm & 231 nm as analytical wavelength for simultaneous estimation. Both the drugs followed Beer's law in concentration range of 8-22mcg/ml. The method was validated in terms of linearity, accuracy (% Recovery), precision (inter day, intraday and reproducibility) and robustness. Linearity of the method was within range (R 2 = 0.999 for both the drugs) and the % recovery was 99.04% for atorvastatin & 100.94% for glimepiride from the binary mixture. The method was found precise (% RSD< 2%) and robust. Commercial products were analyzed by the proposed method and potency was found within limit. Therefore the proposed method can be used for the simultaneous determination of atorvastatin and glimepiride from combined pharmaceutical dosage form.
... Literature survey reveals that several methods have been developed for the quantitative determination of glimepride in plasma and urine. These include HPLC [3][5][6] and LC [4], UV spectrophotometry [7] and HPTLC [8]. The aim of our present study was to calculate the percent assay different brands of Glimepride. ...
Article
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Glimepride belongs to sulfonylurea oral anti diabetic. A efficient least time consuming and simple spectrophotometric method for the assay of Glimepride has been used. The assay is based on the ultraviolet UV absorbance maxima at about 200nm wavelength of Glimepride using water as solvent. A sample of drug was dissolved in water to produce a solution containing Glimepride. Similarly, various dilutions were made. The absorbance of sample preparation was measured at 200nm against the solvent blank and the assay was determined. In our study a simple and quick assay method using U.V spectrophotometer has been used. The assay is based on measuring the absorbance of formulation of Glimepride dilutions at the wavelength of 200 nm. Four different dilutions of 50ppm, 25ppm, 12.5ppm and 6.25ppm is prepared and their percent assay is calculated.
... It is given orally for the treatment of type 2 diabetes mellitus [17]. A literature survey revealed that few liquid chromatography [18,19] and derivative spectrophotometry [18][19][20] methods has been developed for the determination of glimepiride in pharmaceutical formulations. Spectrophotometry [21][22] and Liquid chromatography [23][24][25] methods have also been developed for the estimation of glimepiride in combination with other drugs in pharmaceutical formulations. ...
... Various spectrophotometric methods [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] have been reported for the determination of glimepiride in pure as well as in dosage forms. Most spectrophotometric methods employ ion-pair extraction procedures. ...
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ABSTRACT Objective: A simple, direct and accurate spectrophotometric method has been developed for the determination of glimepiride (GLM) in pure and pharmaceutical formulations by complex formation with bromocresol green (BCG). Methods: The method involves the formation of a yellow ion-pair complex between bromocresol green reagent with glimepiride (C24H34N4O5S); after reacted it with Na2CO3 to give C24H33N4H+O5NaS in chloroform at pH≤3.8. Results: The formed complex was measured at λmax 416 nm against the reagent blank prepared in the same manner. Variables were studied in order to optimize the reaction conditions. Beer’s law was obeyed in the concentration range of 0.981-9.812 μg/ml in the present of 1x10-4 mol/l of (BCG) and 9.812-58.874 μg/ml in the present of 1x10-3 mol/l of (BCG) with good correlation coefficient (R2= 0.9992 and R2= 0.9997, respectively). The relative standard deviation did not exceed 3.0%. The limit of detection (LOD) and the limit of quantification (LOQ) were 0.088 and 0.29 μg/ml, respectively. The proposed method was validated for specificity, linearity, precision and accuracy, repeatability, sensitivity (LOD and LOQ), and robustness with average recovers 98.9 to 102.4%. Conclusion: The developed method is applicable for the determination of glimepiride in pure and different dosage forms with average assay of marketed formulations 97.8 to 102.4% and the results are in good agreement with those obtained by the RP-HPLC reference method.
... Many analytical methods have been reported for the determination of glimepiride. Altinöz and Tekeli (2001) used a simple derivative UV spectrophotometric method for the determination of glimepiride in pharmaceutical tablets. Fahim et al. (2014) described a transmission Fourier transform infrared spectroscopy (FTIR) technique for analysis of metformin and glimepiride in drug samples. ...
Article
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Glimepiride is one of the most widely prescribed antidiabetic drugs and contains both hydrophobic and hydrophilic functional groups in its molecules, and thus could be analyzed by either reversed-phase high performance liquid chromatography (HPLC) or hydrophilic interaction liquid chromatography (HILIC). In the literature, however, only reversed-phase HPLC has been reported. In this study, a simple, rapid and accurate hydrophilic interaction liquid chromatographic method was developed for the determination of glimepiride in pharmaceutical formulations. The analytical method comprised a fast ultrasound-assisted extraction with acetonitrile as a solvent followed by HILIC separation and quantification using a Waters Spherisorb S5NH2 hydrophilic column with a mobile phase consisting of acetonitrile and aqueous acetate buffer (5.0 mM). The retention time of glimepiride increased slightly with decrease of mobile phase pH value from 6.8 to 5.8 and of acetonitrile content from 60% to 40%, indicating that both hydrophilic, ionic, and hydrophobic interactions were involved in the HILIC retention and elution mechanisms. Quantitation was carried out with a mobile phase of 40% acetonitrile and 60% aqueous acetate buffer (5.0 mM) at pH 6.3, by relating the peak area of glimepiride to that of the internal standard, with a detection limit of 15.0 μg/L. UV light absorption responses at 228 nm were linear over a wide concentration range from 50.0 μg/L to 6.00 mg/L. The recoveries of the standard added to pharmaceutical tablet samples were 99.4–103.0% for glimepiride, and the relative standard deviation for the analyte was less than 1.0%. This method has been successfully applied to determine the glimepiride contents in pharmaceutical formulations.
... The standard addition method, taught through analytical chemistry text books as a calibration method to be used when matrix effects cannot be eliminated by physical means, has been widely used in spectrophotometric analysis, especially in atomic spectroscopy [13][14][15][16]. Some atomic spectroscopic instruments such as graphite furnace AAS, are equipped with hardware and software to carry out the standard addition on-line. ...
Article
With mass spectrometric detection in liquid chromatography, co-eluting impurities affect the analyte response due to ion suppression/enhancement. Internal standard calibration method, using co-eluting stable isotope labelled analogue of each analyte as the internal standard, is the most appropriate technique available to correct for these matrix effects. However, this technique is not without drawbacks, proved to be expensive because separate internal standard for each analyte is required, and the labelled compounds are expensive or require synthesising. Traditionally, standard addition method has been used to overcome the matrix effects in atomic spectroscopy and was a well-established method. This paper proposes the same for mass spectrometric detection, and demonstrates that the results are comparable to those with the internal standard method using labelled analogues, for vitamin D assay. As conventional standard addition procedure does not address procedural errors, we propose the inclusion of an additional internal standard (not co-eluting). Recoveries determined on human serum samples show that the proposed method of standard addition yields more accurate results than the internal standardisation using stable isotope labelled analogues. The precision of the proposed method of standard addition is superior to the conventional standard addition method.
... Derivative spectrophotometry was first suggested during the last decade and soon became a well established technique for the assay of drug in mixtures and in pharmaceutical dosage forms [18]. It is a good technique and capable of enhancing the resolution of overlapped bands [19]. ...
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Simple, accurate, sensitive and validated UV spectrophotometric and chemometric methods were developed for the determination of imidapril hydrochloride (IMD) in the presence of both its alkaline (AKN) and oxidative (OXI) degradation products and in its pharmaceutical formulation. Method A is the fourth derivative spectra (D4) which allows the determination of IMD in the presence of both AKN and OXD, in pure form and in tablets by measuring the peak amplitude at 243.0 nm. Methods B, C and D, manipulating ratio spectra, were also developed. Method B is double divisor-ratio difference spectrophotometric one (DD-RD) by computing the difference between the amplitudes of IMD ratio spectra at 232 and 256.3 nm. Method C is double divisor-first derivative of ratio spectra method (DD-DR1) at 243.2 nm, while method D is mean centering of ratio spectra (MCR) at 288.0 nm. Methods A, B, C and D could successfully determine IMD in a concentration range of 4.0–32.0 µg/mL. Methods E and F are principal component regression (PCR) and partial least-squares (PLS), respectively, for the simultaneous determination of IMD in the presence of both AKN and OXI, in pure form and in its tablets. The developed methods have the advantage of simultaneous determination of the cited components without any pre-treatment. The accuracy, precision and linearity ranges of the developed methods were determined. The results obtained were statistically compared to that of a reported HPLC method, and there was no significant difference between the proposed methods and the reported method regarding both accuracy and precision.
... Comprehensive literature survey revealed that quite a few diverse methods have been reported for qualitative and quantitative analysis of GLM in biological samples plasma/serum/urine and in pharmaceutical formulations containing single drug as well as in combination with other drugs. These include miceller electrokinetic capillary chromatography (MEEC) with diode-array detection (DAD) or ultraviolet (UV) detection (Nunez et al. 1995;Roche et al. 1997), high-performance liquid chromatography (HPLC) with DAD (Drummer et al. 1993) and UV detection (Jingar et al. 2008) and derivate UV spectrometric detection (Altinoz and Tekeli 2001), using semimicro bore high-performance liquid chromatography with column switching (Song et al. 2004), with pre-column derivatization (Lehr and Damm 1990), using monolithic column and flow program (El Deeb et al. 2006), HPLC-first derivative spectroscopy (Khan et al. 2009), reverse-phase high performance column chromatography (RP-HPLC, Sujatha et al. 2011;Wanjari and Gaikwad 2005), other HPLC methods (Kovaríkova et al. 2004;Lydia et al. 2005), liquid chromatography-electrospray ionizationtandem mass spectrometry (LC-ESI-MS, Kim et al. 2004a, b;Salem et al. 2004), liquid chromatographymass spectroscopy (LC-MS, Chang et al. 2004;Yuzuak et al. 2007), and other liquid chromatographic techniques (Pathare et al. 2007;Sukumar et al. 2005), thin layer chromatography (TLC) (Valentina et al. 2013;Gumieniczeka et al. 2009), polarographic determination (Ma et al. 2005), square-wave voltammetric technique (Suslu and Altinoz 2011). Methods have also been developed for the estimation of GLM in combination with other drugs simultaneously in pharmaceutical formulations by RP-HPLC techniques (Deepti et al. 2008;Ravi et al. 2011;El-Enany et al. 2012). ...
Article
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There are many analytical methods available for estimation of glimepiride in biological samples and pharmaceutical preparations. To our knowledge, there is no specific reverse-phase high-performance liquid chromatography (RP-HPLC) method for estimation of glimepiride and its dissolution study in self-nanoemulsifying powder (SNEP) formulation. A simple method was carried out on a 5-μm particle octadesyl silane (ODS) column (250 × 4.6 mm) with acetonitrile: 0.2 M phosphate buffer (pH = 7.4) 40:60 v/v as a mobile phase at a flow rate of 1 mL/min, and quantification was achieved at 228 nm using PDA detector. The correlation coefficient (r 2) was found to be 0.999 over the concentration range of 0.2 to 2 μg/mL for glimepiride. The method was validated for linearity, accuracy, and precision. The limit of detection and limit of quantification were found to be 0.38 and 1.17 μg/mL, respectively. The proposed method was found to be simple, precise, suitable, and accurate for quantification of glimepiride as an alternative to the existing methods for the routine analysis of glimepiride in pharmaceutical formulations and in vitro dissolution studies.
... Fig. 1). Many chromatographic [22][23][24], and spectrophotometric methods [25][26][27][28][29][30][31] were also reported for determination of glimepiride either alone or in combination with other antidiabetic drugs. To the best of our knowledge and comprehensive survey, metformin, gliclazide and glimepiride mixture in dosage form was not determined before by RP-HPLC despite their synergistic action. ...
Article
A N separation ISOCRATIC and estimation RP-HPLC of method three has antidiabetics been developed drugs, for metformin, rapid and gliclazide simultaneous and glimepiride in tablet dosage forms within 6 minutes. Separation was carried out on a Thermo Scientific ® BDS Hypersil C 8 column (5µm, 2.50 x 4.60 mm) using a mobile phase of MeOH: 0.025M KH 2 PO 4 adjusted to pH 3.20 using ortho - phosphoric acid (70: 30, v/v) at ambient temperature. The flow rate was 1 mL/min and UV detection was set at 235 nm. The retention time of metformin, gliclazide and glimepiride was noted to be 3.06, 4.33 and 6.00 minutes respectively, indicating a very short analysis time rather than other reported methods. Also, limits of detection were reported to be 0.05, 1.21 and 0.11 µg/mL for metformin, gliclazide and glimepiride, respectively, showing a high degree of the method sensitivity. The method was then validated according to ICH guidelines where it was found to be accurate, reproducible and robust. Finally, the method was compared statistically with reference methods indicating that there is no significant difference between them in respect of precision and accuracy.
... Literature survey revealed that several analytical methods have been reported, such as ultraviolet spectrophotometry [10] , high-performance liquid chromatography (HPLC) [11,12] , liquid chromatographymass spectrometry (LC-MS) [13] and stability study [14] for the estimation of GLM either individually and in combination with other drugs and similarly for EZE [15][16][17] . Few HPLC methods were reported for the simultaneous estimation of EZE and GLM in literature. ...
Article
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Chromatographic separation was achieved with a Shimadzu’s high performance liquid chromatograph and PhenomenexL1 analytical C18 column with a mobile phase of acetonitrile:ammonium acetate buffer (30 mM):methanol (50:45:5 %, v/v/v). The flow rate was set at 1.5 ml/min and the detection wavelength was 232 nm. Quality by design approach was employed for optimization of method parameters like proportion of mobile phase, concentration of buffer and a model highlighting the design space was generated. This developed chromatographic method gave well resolved symmetric peaks. Ezetimibe and glimepiride were eluted at 6.7 and 4.4 min, respectively. This method was validated according to International Conference on Harmonisation Q2(R1) guideline. The method was linear in range of 50-400 µg/ml for ezetimibe and 5-40 µg/ml for glimepiride with r2 =0.9999 and 0.9996, respectively. The sample recoveries were in good agreement with the respective label claim, which suggested non-interference from formulation additives in the estimation. Forced degradation studies were carried out and the stressed samples were analysed using the developed methods.
... Glimepiride lowers blood glucose by stimulating the release of insulin from functioning pancreatic cells [2]. Various spectrophotometric methods [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] have been reported for the determination of glimepiride in pure as well as in dosage forms. ...
Article
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To develop accurate, fast, simple and precise reversed-phase high-pressure liquid chromatography method for simultaneous determination of the binary mixture of glimepiride and pioglitazone HCl in Glimepiride plus 4 mg/30 mg tablets. The chromatographic separation was conducted on Agilent 1200 with DA detector using Luna C18 (150mm x 4.6mm; 5-µm) as stationary phase. Isocratic mobile phase consisted of Phosphate Buffer pH 3.0 : Acetonitrile in ratio (45:55 v/v); The buffer solution is composed of 6.8 gm of potassium dihydrogen orthophosphate in 900 ml adjust pH to 3.0 by ortho-phosphoric acid then complete to 1000 ml by water and filtered through 0.45 μm nylon membrane filter. The flow rate of 1.0 ml min-1 was used. An injection volume of 20 µL was used for both glimepiride and pioglitazone HCl. The detection wavelength (λ max) was 228 nm using a diode array detector. Linearity of the method was established over the concentration ranges of 4.0-12.0 µg ml-1 for glimepiride, with a retention time of 6.90 minutes and 30.0-90.0 µg ml-1 for Pioglitazone HCl, with a retention time of 2.36 minutes. Correlation coefficients were greater than 0.999. The relative standard deviation (RSD) was found to be < 2. The method was fast, accurate, precise, and sensitive hence it can be employed for routine quality control of tablets containing both drugs in quality control laboratories and pharmaceutical industries.
... Literature survey revealed that several analytical methods have been reported, such as ultraviolet spectrophotometry [10] , high-performance liquid chromatography (HPLC) [11,12] , liquid chromatographymass spectrometry (LC-MS) [13] and stability study [14] for the estimation of GLM either individually and in combination with other drugs and similarly for EZE [15][16][17] . Few HPLC methods were reported for the simultaneous estimation of EZE and GLM in literature. ...
... The developed method was applied to determine the valsartan and glimepiride in pharmaceutical formulations. The results obtained were compared with UV-spectrophotometric method given in the literature (Altinoz and Tekeli, 2001). ...
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In this work an electrochemical behavior quantification and interaction of valsartan and glibenclamide were studied using square wave voltammetric technique. The effect of temperature on the interaction was investigated and the thermodynamic parameters (∆H, ∆S & ∆G) were calculated for the interaction and binding constant (K) also obtained. The calibration curves of each drug were linear within the range of concentration [(4.99×10-7) – (6.95×10-6)], [(5.96×10-8) – (1.15×10-6)] molar with R2 value equal to 0.9819, 0.9926 for valsartan and glibenclamide respectively.
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A new, simple, precise, and accurate high performance thin layer chromatography (HPTLC) densitometry method has been developed for simultaneous estimation of rosiglitazone maleate (ROSI) and glimepiride (GLIM) in tablet dosage form. Procedure does not require prior separation of components from the sample. Chromatographic separation of the drugs was performed on aluminum plates precoated with silica gel 60 F254 as the stationary phase and the solvent system consisted of methanol: toluene: ethyl acetate (1:8:1, v/v/v). Densitometric evaluation of the separated zones was performed at 228 nm. The drugs were satisfactorily resolved with Rf values 0.39 ± 0.03 and 0.20 ± 0.04 for ROSI and GLIM, respectively. Parameters such as linearity, precision, accuracy, recovery, specificity, and ruggedness were studied as reported in the International Conference on Harmonization (ICH) guidelines. The linearity regression analysis for calibration showed correlation coefficients R2 valve 0.9989 and 0.9996 for ROSI and GLIM, respectively with respect to peak area in the concentration range of 100-1500 ng/spot. The mean percentage recovery values were close to 100 %, it indicates that there is no interferences of additives with ROSI and GLIM present in tablet dosage form. Statistical analysis proved that the method is suitable for the quality control analysis of ROSI and GLIM as a bulk drug and in pharmaceutical formulations. The study may be extended to comprehend the degradation kinetics of these two drugs.
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Glimepiride is an oral antidiabetic drug widely used in treatment of type 2 diabetes. This work proposed the development and validation of a derivative UV spectrophotometric method for determination of glimepiride in tablets. The quantification of glimepiride in 5×10-3 mol L-1 NaOH was performed by using a wavelength interval of 8 nm in the range of 220-300 nm. The amplitude values obtained in the second-derivative spectra were arbitrary units of the peak height from the central zero base line to the signals obtained at 279.0, 257.5 and 256.3 nm for quantification of Amaryl® tablets 1 mg, Amaryl® tablets 2 mg and Amaryl® tablets 4 mg, respectively. The method was completely validated according to the International Conference on Harmonization (ICH) guidelines, showing accuracy, precision, selectivity, robustness and linearity. The validated method is suitable for quality control applications, since it does not use polluting reagents, it is simple and has low-cost.
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Five simple and sensitive methods were developed for the determination of tofisopam (TF). The first four are stability-indicating depending on the determination of TF in the presence of its degradation product, while the fifth depended on the determination of TF via its degradation product. Method A was based on first and second derivative spectrophotometry, 1D and 2D, measuring the amplitude at 298 and 332 nm in the case of 1D and at 312 and 344 nm in the case of 2D. Method B depended on measuring the peak amplitude of the first derivative of the ratio spectra 1DD at 336 nm. Method C was based on difference spectrophotometry by measuring ΔA at 366 nm. Method D was a TLC method using silica gel 60 F254 plates, the optimized mobile phase ethyl acetate–methanol–ammonium hydroxide 10% (8.5 + 1.0 + 0.5, v/v/v), and quantification by densitometric scanning at 315 nm. In method E, spectrofluorometry was applied for the determination of TF via its degradation product; maximum emission was 383 nm when excitation was 295 nm. Linearities were obtained in the concentration range 2–20 μg/mL for methods A, B, and C and 2–20 μg/band and 0.2–1.6 μg/mL for D and E, respectively. In method A, the mean recoveries were 99.45 ± 0.287 and 100.28 ± 0.277% at 298 and 332 nm, respectively, in the case of 1D and 99.40 ± 0.245% and 99.50 ± 0.292% at 312 and 344 nm, respectively in the case of 2D. The mean recovery was 100.03 ± 0.523% at 366 nm in method B. Method C showed mean recovery of 100.20 ± 0.642%. Recoveries for methods D and E were 98.98 ± 0.721 and 100.25 ± 0.282%, respectively. The degradation product was obtained in acidic stress condition, separated, and identified by IR and mass spectral analysis, from which the degradation product was confirmed and the degradation pathway was suggested. The first four methods were specific for TF in the presence of different concentrations of its degradation product. The five proposed methods were successfully applied for the determination of TF in Nodeprine tablets. Statistical comparison among the results obtained by these methods and that obtained by the official method for the determination of the drug was made, and no significant differences were found.
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In this study, glimepiride and L-arginine (GA) binary mixtures at various molar ratios were prepared to evaluate whether they could improve the poor water solubility and dissolution characteristics of glimepiride. It was shown that glimepiride and arginine form a eutectic mixture, a type of crystalline solid dispersions, at a 1:1 molar ratio and eutectic temperature of 426.9 K using a phase diagram constructed using differential scanning calorimetry (DSC) and thermo-microscopy. The preserved characteristic powder X-ray diffraction (PXRD) patterns and infrared (IR) spectra of each material in those of GA binary mixtures confirmed the formation of eutectic mixture without molecular interaction in solid state. The formation of GA eutectic mixture (GAEM) resulted in the improvement of solubility through pH modification and the intermolecular interaction of glimepiride and L-arginine in aqueous mediums, thereby wettability and dissolution rate of glimepiride were also enhanced. The intermolecular interaction between glimepiride and L-arginine at a 1:1 stoichiometry of the complex in solution state was identified by phase solubility, stoichiometric determination, and solution state nuclear magnetic resonance (NMR) spectroscopy. Specific molecular interactions such as hydrogen bonding and hydrophobic interaction were suggested as main mechanisms of GA complexation in solution. Therefore, this study concludes that the GAEM could be an effective way to improve the solubility and dissolution rate of glimepiride.
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This paper describes the multivariate development of a stability-indicating HPLC method for the quantification of glimepiride in pharmaceutical tablets. Full factorial design, Doehlert design, and response-surface methodology were used in conjunction with the desirability function approach. This procedure allowed the adequate separation of glimepiride from all degradant peaks in a short analysis time (about 9 min). This HPLC method uses potassium phosphate buffer (pH 6.5; 27.5 mmol/L)-methanol (34 + 66, v/v) mobile phase at a flow rate of 1.0 mL/min and UV detection at 228 nm. A Waters Symmetry C18 column (250 x 4.6 mm, 5.0 pm) at controlled room temperature (25 degrees C) was used as the stationary phase. The method was validated according to International Conference on Harmonization guidelines and demonstrated linearity from 2 to 40 mg/L glimepiride, selectivity, precision, accuracy, and robustness. The LOD and LOQ were 0.315 and 1.050 mg/L, respectively. The multivariate strategy adopted in this work can be successfully applied in routine laboratories because of its fast optimization without the additional cost of columns or equipment.
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The objective of present study was to develop and validate an analytical method for quantitative determination and dissolution studies of glimepiride in tablets. The glimepiride shows absorption maxima at 225 nm and obeyed Beer's law in the range of 6.0 – 14.0 µg/mL. The limit of detection and limit of quantitation were 0.06, and 0.17 µg/mL respectively. Percentage recovery of glimepiride for the proposed method ranged from 99.32 to 100.98% indicating no interference of the tablet excipients. It was concluded that the proposed method is simple, easy to apply, economical and used as an alternative to the existing spectrophotometric and non-spectrophotometric methods for the routine analysis of glimepiride in pharmaceutical formulations and in vitro dissolution studies.
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A simple, specific, accurate and economical gradient reversed phase liquid chromatographic (RP-HPLC) method was developed and subsequently validated for the determination of glimipiride, rosiglitazone and pioglitazone hydrochloride. Separation was achieved with a nucleodur C–18 column having 250×4.6 mm i.d. with 5 µm particle size and water HPLC grade adjusted to pH 3.0 using diluted orthophosphoric acid and acetonitrile (80:20 v∕v) with gradient program as eluent at a constant flow rate of 0.8 ml per min. UV detection was performed at 215 nm. The retention time of glimipiride, rosiglitazone and pioglitazone hydrochloride were about 17.9 min, 6.31 min and 8.24 min respectively. This method is simple, rapid and selective and can be used for routine analysis of antidiabetic drugs in pharmaceutical preparation. The proposed method was validated and successfully used for estimation of glimipiride, rosiglitazone and pioglitazone hydrochloride in the pharmaceutical dosage form.
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Two rapid, simple, accurate and sensitive spectrophotometric methods were developed for the determination of glimepiride in pharmaceutical preparations. The first method was based on the formation of a charge-transfer complex of the drug, as n-electron donor, with 7,7,8,8-tetracyanoquinodimethane (TCNQ), as π-acceptor. The second method was based on the formation of ion-pair complexes between the examined drug and bromothymol blue (BTB). The proposed methods were validated for linearity, limit of detection, limit of quantification, precision, accuracy, robustness and specificity. The calibration was linear over the concentration range of 10–80 and 20–120 μg/mL for methods I and II, respectively. The limits of detection were 2.6 and 2.8 μg/mL. The proposed methods were applied to the determination of the drug in pharmaceutical preparations. The results obtained were in good agreement with those obtained using the reference method (HPLC). There was no significant difference in the accuracy and precision as revealed by the accepted values of t- and F-tests, respectively.
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A simple, high performance liquid chromatographic method has been developed for the simultaneous determination of glipizide, rosiglitazone, pioglitazone, glibenclamide and glimepiride in pharmaceutical dosage forms and human plasma. The elution was performed using a mobile phase mixture of 0.05% Triethylamine (pH-3.5, adjusted with ortho phosphoric acid), acetonitrile and methanol in the ratio of 55:15:30 at a flow rate of 1 ml min−1 on a phenomenex C18 column (150 × 4.6 mm, i.d., 5 μm) at ambient temperature. The drugs were monitored at a wavelength of 248 nm and were separated within 20 min. Mixtures of formulations were prepared in suitable dilutions and plasma samples were prepared by extraction with acetonitrile. The method was successful in detecting the drugs at a concentration of less than 0.1 μg ml−1 for each drug and %RSD for intra- and inter-day studies was found to be less than 4.34 for all the selected concentrations. Moreover, the method was validated as per ICH guidelines and the results were found to be within the acceptable range. Hence, the proposed method can be used for the routine quality control of the drugs and can also be applied to pharmacokinetic studies.
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An innovative spectrophotometric method was developed for simultaneous determination of compounds with interfering spectra in binary mixtures without previous separation, showing significant advantages over the conventional methods regarding minimal data manipulation and applicability. The proposed method was applied for the determination of retinoic acid and hydroquinone in laboratory-prepared mixtures with mean percentage recoveries 100.13 ± 0.31 and 99.99 ± 0.04, respectively, and in their pharmaceutical formulation with mean percentage recoveries 100.13 ± 0.86 and 100.07 ± 0.58, respectively. The method was validated according to USP guidelines and can be applied for routine quality control testing.
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Glimiperide is an anti-diabetic drug which is used for the treatment of diabetes. In present work, a simple, sensitive, accurate and economical spectroscopic method has been developed for the estimation of glimepiride in bulk and in pharmaceutical dosage forms. An absorption maximum was found to be at 249 nm with the solvent system of chloroform. The drug follows Beer's law limits in the range of 5-30 µg/ml with correlation coefficient of 0.999732. Results of the analysis were validated for accuracy, precision, LOD were found to be satisfactory. The proposed method is simple, rapid and suitable for the routine quality control analysis.
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The present study involves designing and develop of a bilayer tablets of glimepiride (GLP) and metformin HCl (MHCl) to offer immediate release of GLP and sustained release of MHCl. Bilayer tablets consists of two layers, i.e immediate release layer made by using superdisintegrant sodium starch glycolate and sustained release layer designed as matrix formulations with polymers polyethyleneoxide and polyvinylpyrrolidone to modulate the drug release. Wet granulation method was employed to make bilayer tablets. Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD) and Differential scanning calorimetry (DSC) were used for the physicochemical compatibility and stability study of the tablets. Accelerated stability studies were followed in compliance with ICH guidelines. The in-vitro release profile shows desired biphasic release behaviour. GLP was dissolved in 45 min and MHCl releases up to 12 h. FTIR, XRD and DSC data for the final formulations indicate good compatibility and stability. These tablets exhibit no change either in physical appearance or dissolution pattern after storage at accelerated condition (40±2°C / 75±5%RH) for 6 months. Therefore, biphasic drug release pattern was successfully achieved through the formulation of bilayer tablets that are stable and capable of releasing the drug over 12 h.
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In the present work, the thermal decomposition of glimepiride (sulfonylurea hypoglycemic agent) was studied using differential scanning calorimetry (DSC) and thermogravimetry/derivative thermogravimetry (TG/DTG). Isothermal and non-isothermal methods were employed to determine kinetic data of decomposition process. The physical chemical properties and compatibilities of several commonly used pharmaceutical excipients (glycolate starch, microcrystalline cellulose, stearate, lactose and Plasdone) with glimepiride were evaluated using thermoanalytical methods. The 1:1 physical mixtures of these excipients with glimepiride showed physical interaction of the drug with Mg stearate, lactose and Plasdone. On the other hand, IR results did not evidence any chemical modifications. From isothermal experiments, activation energy (Ea) can be obtained from slope of lnt vs. 1/T at a constant conversion level. The average value of this energy was 123 kJ mol–1. For non-isothermal method Ea can be obtained from plot of logarithms of heating rates, as a function of inverse of temperature, resulting a value of 157 and 150 kJ mol–1, respectively, in air and N2 atmosphere, from the first stage of thermal decomposition.
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An analytical method based on liquid chromatography–tandem mass spectrometry (LC-MS-MS) was developed and validated for the determination of glimepiride in human plasma. Glimepiride and glimepiride-d4 (internal standard) were extracted from the plasma by solid phase extraction and chromatographed on a C18 analytical column using an isocratic mobile phase. Detection was carried out by positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode. The chromatographic separation was obtained within 2 min. Linearity was established from 1.00–500.00 ng/mL with a coefficient of determination (r2) of 0.9981 or greater. The lower limit of quantitation (LOQ) was identifiable and reproducible at 1.00 ng/mL with a precision of 3.8%. The method has shown remarkable reproducibility, with intra- and inter-day precision and accuracy
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Electrochemical behavior and differential pulse polarographic analysis (DPPA) of rosuvastatin (RSV) in pure form and in pharmaceutical preparations using dropping mercury electrode (DME) with di-sodium hydrogen orthophosphate buffer at pH0.5 was applied. One redaction peak was observed in the range -1081 to -1094 mV (Ep). The peak current Ip is linear over the ranges 0.0963-24.077 μg.mL-1. The DPPA has been used successfully for the determination of RSV in pure form and in pharmaceutical formulations. The relative standard deviation did not exceed 4.0% for the concentrations of RSV 0.0963 μg.mL-1. Regression analysis showed a good correlation coefficient (R2= 0.9998) between Ip and concentration over the mentioned range. The limit of detection (LOD) and the limit of quantification (LOQ) were to be 0.0125 and 0.038 μg.mL-1, respectively. The proposed method was successfully applied to the analysis of RSV in pure and pharmaceutical dosage forms with average recovery of 95.0 to 103.95%. The results obtained agree well with the contents stated on the labels.
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In the present study a simple, precise, accurate and reproducible spectrophotometric method has been developed and validated for the quantification of rosuvastatin calcium and glimepiride in solid dosage form by simultaneous equation method. This method uses the spectrum mode of analysis of Simardzu spectrophotometer (UV 1601 and 1240) and utilizes 241 nm and 231 nm as analytical wavelengths for simultaneous estimation. Both the drugs followed Beer's law in concentration range of 10-22µg/ml. The method was validated in terms of linearity (within 10-22µg/ml), accuracy (% Recovery), precision (inter day and intraday) reproducibility (UV model-1601 and 1240) and robustness. Linearity of the method was with in range and the % recovery was 99.04% for rosuvastatin calcium and 100.94% for glimepiride from the binary mixture. The method was found precise (% RSD< 2%). and robust. Therefore the proposed method is suitable and can be adopted for the simultaneous determination of rosuvastatin calcium and glimepiride from combined pharmaceutical dosage form in routine quality control analysis.
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Glimepiride is a third generation sulphonylurea antidiabetic drug. It shows low, pH dependent solubility thus is classified as class II drug according to Biopharmaceutics Classification Systems (BCS). The poor solubility of the drug may cause poor dissolution and unpredicted bioavailability. Scientists can ask for biowaivers in case of Class I compounds if they are formulated as immediate release oral dosage forms. Class II drugs are also the candidates for a waiver of bioequivalence and bioavailability studies. In the present study developed dissolution medium was easy to prepare, stable over a longer period, simple and cost-effective. In vitro dissolution test was performed using 2% SLS as the medium of dissolution in USP apparatus II (paddle) at 100 rpm, for glimepiride tablet could reliably discriminate among different products. Drug release was found above 95% within 30 min. To explain the kinetics of released drug contents, various statistical models including First-order, Zero-order Higuchi’s, Hixson-Crowell’s, and Weibull’s were used. Glimepiride was best fitted to the Weibull’s kinetics. Furthermore, goodness-offit test, the mean square error and the Akaike Information Criterion were used for selection of appropriate model; f2 test was applied for comparison of similarity between the release profile of various trial marketed brands. © Latin American Journal of Pharmacy 2014. All Rights Reserved.
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Background In some cases, lifestyle changes are not enough to keep type 2 diabetes under control, there are several medications that may help. Metformin can lower your blood sugar levels. Glimepiride, make more insulin. Empagliflozin, prevent the kidneys from reabsorbing sugar into the blood and sending it out in urine. Methods Mean centering, double divisor, ratio spectra-zero crossing, and successive derivative were applied for estimation of metformin, empagliflozin, and glimepiride respectively, in their prepared laboratory mixtures and in pharmaceutical tablets, without prior chemical separation. The absorption spectra of the mentioned drugs were recorded in the range of 200-400nm. Results These methods were linear over the concentration ranges of 1.0-10, 2.5-30, and 1.0-10 µgmL-1 of metformin, empagliflozin, and glimepiride respectively. Mean centering for metformin were measured at 234 and 248 nm, empagliflozin and glimepiride had amplitude values at 276 and 262 nm, respectively. The derivative of double divisor was measured at 234, 278, and 288 nm for metformin, empagliflozin and glimepiride, respectively. The ratio spectra-zero crossing was quantifying at the amplitude values of the analytical signal at 234 and 274 nm for metformin and empagliflozin, respectively, whereas glimepiride was determined at 242 and 286 nm. The successive ratio of metformin, empagliflozin, and glimepiride were determined at 284, 242, and 266 nm, respectively. Conclusion The methods are validated according to the ICH guidelines where accuracy, precision and repeatability are found to be within the acceptable limit. The methods were studied and optimized, upon the validation linearity, precision, accuracy, LOD, LOQ and selectivity were proved to be operative for analysis of the specified drugs in pharmaceutical dosage configuration. The statistical illustration was done between the suggested methods with the reported methods with consideration to accuracy and precision no significant difference was found by student’s t-test, F-test and one-way ANOVA.
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An isocratic reversed-phase high-performance liquid chromatography (RP-HPLC) method has been developed for rapid and simultaneous separation and estimation of 3 antidiabetic drugs, namely, metformin, pioglitazone, and glimepiride, in human plasma within 3 min. Separation was carried out on a MAGELLEN 5U C 18 (5 μm, 150 mm × 4.60 mm) using a mobile phase of MeOH–0.025 M KH 2 PO 4 adjusted to pH 3.20 using ortho -phosphoric acid (85:15, v / v ) at ambient temperature. The flow rate was 1 mL/min, and the maximum absorption was measured at 235 nm. The retention time of metformin, pioglitazone, and glimepiride was noted to be 1.24, 2.32, and 2.77 min, respectively, indicating a very short analysis time compared to that of other reported methods. Also, limits of detection were reported to be 0.05, 0.26, and 0.10 μg/mL for metformin, pioglitazone, and glimepiride, respectively, showing a high degree of method sensitivity. The method was then validated according to the FDA guidelines for the determination of the three drugs clinically in human plasma, in particular, regarding pharmacokinetic and bioequivalence simulation studies.
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A simple, direct and accurate spectrophotometric method has been developed for the determination of Glimepiride (GLM) in pure and pharmaceutical formulations by complex formation with bromocresol purple (BCP). The method involves the formation of a yellow ion-pair complex between BCP with glimepiride at pH<3,8; after reacting GLM with Na2CO3 to give C24H33N4H+O5NaS which is extracted by chloroform. The formed complex [GLM]:[ BCP] was measured at lmax 418 nm against the reagent blank prepared in the same manner. Variables were studied in order to optimize the reaction conditions. Molar absorptivity (e) for complex was 20600 L.mol-1.cm-1. Beer’s law was obeyed in the concentration range of 1.226 – 46.608 mg.mL-1 in present of 5.0x10-4 mol/l of BCP with good correlation coefficient (R2= 0.9997). The relative standard deviation did not exceed 3.6%. The limit of detection (LOD) and the limit of quantification (LOQ) were 0.15 and 0.46 mg.mL-1, respectively. The proposed method was validated for specificity, linearity, precision and accuracy, repeatability, sensitivity (LOD and LOQ) and robustness. The developed method is applicable for the determination of GLM in pure and different dosage forms with average assay of 98.8 to 102.0% and the results are in good agreement with those obtained by the RP-HPLC reference method.
Article
Trans- and cis-glimepiride were directly separated by a new established high performance chromatographic method, which involved the use of Chirex 3005 column. Several parameters were studied. Simple and reliable separation was achieved, with the separation factor (alpha) 1.12 and the resolution factor (R-s) 1. 86, when using the optimized mobile phase composed of n-hexane: 1,2-dicholoethane: methanol (88/8/4 by vol) at 25degreesC and 1.8 mL/min. Standard linear calibration curve was established for trans-glimepiride, over the range of 3 similar to 320 mg/L, with the correlation coefficient of 1. 0000. The minimum limit of detection was 0. 47 mg/L. Precision of the assay was gratifying and the method has been used to monitor and identify quantitatively the products of glimepiride.
Article
Two new, simple, sensitive, accurate and reproducible spectrophotometric methods were developed for the simultaneous estimation of rosiglitazone maleate and glimepiride in combine dosage form. The methods employed are simultaneous equation method and partial simultaneous equation method. Method I employed generation and solving simultaneous equations using 248.5 and 228.5 nm as two analytical wavelengths and method II employed 312 and 228.5 nm as λ3 and λ2. Both drugs obeyed Beer's law in the concentration ranges of 2 to 16 μg/mL. Statistical analysis and recovery studies validated the method. The method is found to be rapid, precise and accurate and can easily be employed in the laboratory for routine estimation of drugs.
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Two simple and sensitive visible spectrophotometric methods have been developed for the quantitative estimation of glimepiride from its tablet formulation. The developed methods are based on formation of chloroform extractable coloured complex of drug with methylene blue and safranine. The chloroform extracted complex of drug with methylene blue showed absorbance maxima at 652 nm and linearity was observed in the concentration range of 15-50 μg/mL (method-I), with safranine showed absorbance maxima at 536 nm and linearity was observed in the concentration range of 10-80 μg/mL (method-II). Results of analysis for both the developed methods were validated statistically and by recovery studies.
Article
Two simple, accurate and reproducible spectrophotometric methods have been developed and validated for simultaneous estimation of glimepiride and metformin in combined dosage form. Glimepiride shows maximum absorbance at 222 nm and metformin at 228 nm. First method was based on first-order derivative spectroscopy, in which wavelengths selected were 249 nm (zero crossing of metformin) where glimepiride shows considerable absorbance and 258 nm (zero crossing of glimepiride) where metformin shows considerable absorbance. The second method was based on multicomponent mode technique, in which sampling wavelengths selected were 222 and 228 nm. Linearity for detector response was observed in the concentration range of 3-15 μg/mL for glimepiride and 1.0-5.0 μg/mL for metformin for method I; 2.0-10.0 μg/mL for glimepiride and 0.5-2.5 μg/mL for metformin for method II respectively. Accuracy and precision studies were carried out and results were satisfactory. The proposed methods were validated as per ICH guidelines. The developed methods are simple, precise, rugged and economical. The utility of the methods has been demonstrated by analysis of commercially available formulations.
Article
A sensitive method for quantitation of glimepiride in human plasma has been established using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI/MS/MS). Glipizide was used as an internal standard. Glimepiride and internal standard in plasma sample was extracted using diethyl ether-ethyl acetate (1:1). A centrifuged upper layer was then evaporated and reconstituted with the mobile phase of acetonitrile-5 mM ammonium acetate (60:40, pH 3.0). The reconstituted samples were injected into a C18 reversed-phase column. Using MS/MS in the multiple reaction monitoring (MRM) mode, glimepiride and glipizide were detected without severe interference from human plasma matrix. Glimepiride produced a protonated precursor ion ([M+H] +) at m/z 491 and a corresponding product ion at m/z 352. And the internal standard produced a protonated precursor ion ([M+H]+) at m/ z 446 and a corresponding product ion at m/z 321. Detection of glimepiride in human plasma by the LC-ESI/MS/MS method was accurate and precise with a quantitation limit of 0.1 ng/mL. The validation, reproducibility, stability, and recovery of the method were evaluated. The method has been successfully applied to pharmacokinetic studies of glimepiride in human plasma.
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A convenient and sensitive spectrofluorimetric method is described for the determination of two antidiabetic drugs i.e., pioglitazone HC1 and glimepiride, in pharmaceutical formulations and biological fluids. The method is based on the native fluorescence of the studied drugs in methanol. The fluorescence intensity was measured in methanol at 512 and at 522 nm for pioglitazone HC1 excitation and glimepiride, respectively. The effect of some surfactants on the fluorescence intensity was studied. Regression analysis showed good correlation (r = 0.9999) between fluorescence intensity and concentration over the range of 0.005-1.3 μg/mL for pioglitazone HC1 with lower limit of detection (LOD) of 1.61 × 10 -3 μg/mL and 0.01-1.5 μg/mL with (LOD) 3.59 × 10 -3 μg/mL for glimepiride. The studied drugs were successfully determined in their tablets and in biological fluids.
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Currently available methods for the detection of matrix effects in liquid chromatography-mass spectrometry (LC-MS) are tedious and complex; therefore, a simpler method is required. Although there are no methods to completely eliminate matrix effects, the most well-recognized technique available to correct for matrix effects is that of internal standardization using stable isotope-labeled versions of the analytes. As this method can prove expensive, an alternative method of correction is likely to be useful. In this study, a simple method based on recovery is assessed for the detection of matrix effects. Two alternative methods for the rectification of matrix effects in LC-MS are also assessed: standard addition and the coeluting internal standard method.
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A simple, specific, accurate and stability indicating reversed phase high performance liquid chromatographic method was developed for the simultaneous determination of and Metformin Hydrochloride, Rosiglitazone Maleate and Glimepiride in tablet dosage forms. Detector consists of photodiode array detector; the reversed phase column used was RP-C18 (2.27µm size, 250 mm´4.6 mm i.d.) at ambient temperature, in isocratic mode, with mobile phase containing Methnol: Acetonitrile: Phosphate Buffer, pH 5.39 (20: 40: 40 % v/v/v) adjusted to pH 5.39 using ortho phosphoric acid was used. The flow rate was 1.0 ml/min and effluents were monitored at 238 nm. The retention times of Metformin Hydrochloride, Rosiglitazone Maleate and Glimepiride were 3.69 min, 8.18 min and 12.5 min respectively. The calibration curves were linear in the concentration range of 4-24 g/ml for Metformin Hydrochloride, Rosiglitazone Maleate and Glimepiride. The proposed method was validated and successfully applied to the estimation of Metformin Hydrochloride, Rosiglitazone Maleate and Glimepiride in combined tablet dosage forms. Linearity was obtained in the concentration range of 4 to 24 µg/ml of Metformin Hydrochloride, Rosiglitazone Maleate and Glimepiride with a correlation coefficient of 0.9963, 0.9992 and 0.9957 respectively. Detector consists of photodiode array detector; the reversed phase column used was RP-C18 (2.27µm size, 250 mm´4.6 mm i.d.) at ambient temperature. The developed method was validated according to ICH guidelines and values of accuracy, precision and other statistical analysis were found to be in good accordance with the prescribed values. Thus the proposed method was successfully applied for simultaneous determination of Metformin Hydrochloride, Rosiglitazone Maleate and Glimepiride in routine analysis.
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Linezolid (LIN) is considered the first available oxazolidinone antibacterial agent. It is susceptible to hydrolysis and oxidation. Five simple, accurate, sensitive and validated UV spectrophotometric methods were developed for LIN determination in the presence of its alkaline (ALK) and oxidative (OXD) degradation products in bulk powder and pharmaceutical formulation. Method A is a second derivative one (D-2) in which LIN is determined at 240.9 nm. Method B is a pH-induced differential derivative one where LIN is determined using the fourth derivative (D-4) of the difference spectra (Delta A) at 285.3 nm. Methods C, D, and E are manipulating ratio spectra, where C is the double divisor-ratio difference spectrophotometric one (DD-RD) in which LIN was determined by calculating the amplitude difference at 243.7 and 267.6 nm of the ratio spectra. Method D is the double divisor-first derivative of ratio spectra (DD-DD1) in which LIN was determined at 270.2 nm. Method E is a mean centering of ratio spectra one (MCR) in which LIN was determined at 318.0 nm. The developed methods have been validated according to ICH guidelines. The results were statistically compared to that of a reported HPLC method and there was no significant difference regarding both accuracy and precision.
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A simple, precise, and accurate high-performance thin-layer chromatography (HPTLC) method for the simultaneous determination of pioglitazone, metformin, and glimepiride in multicomponent pharmaceutical preparations has been developed and validated. Pioglitazone, metformin, and glimepiride from the formulations were separated on silica gel 60 F(254) HPTLC plates with acetonitrile, methanol, propyl alcohol, and ammonium acetate solutions in the proportion of 7:2:1:1 (v/v) as mobile phase. Densitometric quantification was performed at 240 nm. Well-resolved bands were obtained with R(F). values 0.83, 0.21, and 0.89 for pioglitazone, metformin, and glimepiride, respectively. The method was validated for precision, accuracy, specificity, and robustness. The calibration curve was found to be linear in the concentration range of 0.3-1.2, 10-40, and 0.04-0.16 mu g per band by area with correlation coefficients of 0.995, 0.996, and 0.998 for pioglitazone, metformin, and glimepiride, respectively. The method is selective and specific, with potential application in pharmaceutical analysis of these drugs in bulk and formulations.
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Two new UV-spectrophotometric methods have been developed for simultaneous estimation of rosiglitazone maleate and glimepiride in tablets. The first method was based on application of vierodt's method which involves the formation and solving of simultaneous equations at 247.0 and 228.0 nm, as absorbance maxima of rosiglitazone maleate and glimepiride, respectively. The second method employed was absorption correction method which involves direct estimation of rosiglitazone maleate at 311.5 nm, as at this wavelength glimepiride has zero absorbance and shows no interference. For estimation of glimepiride, corrected absorbance was calculated at 228.0 nm due to the interference of rosiglitazone maleate at this wavelength. Calibration curves were linear with correlation coefficient between 0.99-1.0 over the concentration range of 2-20 µg/mL for both the drugs. The mean percent recovery was found in the range of 99.41-99.80 and 100.36-100.52 for vierodt's method and 99.18-99.80 and 99.64-99.92 for absorption correction method, for rosiglitazone maleate and glimepiride, respectively. The results of analysis were validated statistically and proven to be rugged. The proposed methods are simple, rapid, accurate, precise, economical and can be used successfully in the quality control of pharmaceutical formulations and routine laboratory analysis.
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Glimepiride, 1-{4-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-1-carboxyamido)ethyl]phenylsulfonyl} -3-(trans-4-methylcyclohexyl)urea, C24H34N4O5S, is a drug used in the treatment of non-insulin dependent diabetes mellitus.
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A sensitive and selective high-performance liquid chromatographic method has been developed for a new sulphonylurea, glimepiride, and its metabolites. The assay involves extraction with diethyl ether, thermolysis of the sulphonylureas at 100 degrees C and trapping of the resulting amines with 2,4-dinitrofluorobenzene. The derivatives were quantitated on a reversed-phase column by absorbance at 350 nm using a step gradient for the three compounds in serum and an isocratic run for the metabolites in urine. Analogous compounds were used as internal standards. The detection limit was 5 ng/ml for glimepiride and metabolite II and 10 ng/ml for metabolite I using 1 ml of serum. The method has been applied to the analysis of serum and urine samples from pharmacokinetic studies in humans.
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Although sulfonylurea agents have been used in the clinical management of type II diabetes (non-insulin-dependent diabetes mellitus, NIDDM) for over two decades, the mechanisms responsible for their hypoglycemic action remain controversial. We have quantitated glycemic control, endogenous insulin secretion in response to mixed meals, adipocyte insulin binding, insulin-mediated peripheral glucose disposal, and basal hepatic glucose output in 17 type II diabetic subjects before and after 3 mo of therapy with the second-generation, sulfonylurea compound glyburide in an attempt to identify the factors responsible for the clinical response to the drug. In addition, 9 subjects were treated for an additional 15 mo to see if the response to the drug changed with time. The mean fasting serum glucose level fell from an initial value of 264 +/- 17 mg/dl to 178 +/- 16 mg/dl after 3 mo of drug therapy. Endogenous insulin secretion increased in all subjects, but the increase was most marked in those subjects who continued to exhibit fasting hyperglycemia (fasting serum glucose greater than 175 mg/dl) after 3 mo of therapy. Adipocyte insulin binding was unchanged after 3 mo of therapy, while the maximal rate of peripheral glucose disposal was increased by 23%, indicating enhancement of peripheral insulin action at a postreceptor site(s). Basal hepatic glucose output showed a significant correlation with the fasting serum glucose level both before and after therapy (r = 0.86, P less than 0.001) and fell from 141 +/- 12 mg/m2/min before therapy to 107 +/- 11 mg/m2/min after 3 mo of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
This study evaluates stimulated insulin production rate (incremental AUC x MCR (metabolic clearance rate) of C-peptide) and blood glucose (BG) response after i.v. administration of glimepiride (Hoe 490, GLI, CAS 93479-97-1) (0.25, 0.50, 0.75, 1.00, 1.25, 1.50 mg) in healthy man (27 +/- 4 yrs). It was shown that i.v. bolus administration of GLI (0.25, 0.50, 1.25 and 1.50 mg) caused a dose-related rise in insulin production from 18 +/- 17 to 25 +/- 13, 36 +/- 14 and 54 +/- 34 pmol/kg body weight, respectively. This effect did not yet plateau at 1.5 mg GLI and was paralleled by a fall in BG (decremental area below BG baseline) by 40 +/- 36, 69 +/- 20, 161 +/- 47 and 113 +/- 62 mmol.min/l. It is concluded that insulin release is increased by i.v. GLI in a dose related manner, while a parallel decline in BG was induced only up to 1.25 mg GLI. The less marked fall of BG after injection of 1.50 mg GLI may reflect interference by insulin-counterregulatory hormones secondary to induced hypoglycaemia.
Article
In order to achieve appropriate blood glucose control, the treatment of non-insulin dependent (NIDDM) Type II diabetes usually starts with diet and exercise. If this still results in insufficient metabolic control, oral hypoglycaemic drugs or insulin are added to the non-pharmacological measures. Sulphonylureas have been used successfully as oral hypoglycaemic agents since the 1950s but there are aspects where medication could be better adjusted to the patients' needs. Preclinical investigations on animals and in vitro studies with glimepiride (HOE490), a new sulphonylurea, suggested some benefit over sulphonylureas currently available, including lower dosage, rapid onset and long duration of action, lower insulin and C-peptide levels, possibly due to less stimulation of insulin secretion and more pronounced extrapancreatic effects. The clinical relevance of these findings were studied in clinical trials. 19 phase II and 4 phase III clinical studies, in a total of about 3750 Type II diabetic patients, established efficacy and safety of glimepiride in comparison to placebo and glibenclamide and showed its therapeutic value. 1 mg per day induced a marked blood glucose reduction (FPG 2.4 mmol/l; HbA1c 1.2%) which could be enhanced by increasing the dose to the maximum effective 4 and 8 mg daily. In patients, glimepiride had a more rapid onset of action than glibenclamide, with a long duration of action. Glimepiride achieved metabolic control with the lowest dose (1-8 mg daily) of all the sulphonylureas. In addition, it maintained a more physiological regulation of insulin secretion than glibenclamide during physical exercise, suggesting that there may be less risk of hypoglycaemia with glimepiride.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
The possibility of an insulin-independent blood glucose decreasing activity of sulfonylureas was re-evaluated. Single dose studies in dogs with different sulfonylureas revealed a ranking in the ratio of plasma insulin release/blood glucose decrease with glimepiride exhibiting the lowest and glibenclamide the highest ratio. This ranking suggests that sulfonylureas have extrapancreatic activity and that this is most pronounced for glimepiride. Further evidence for this was derived from single dose studies in rabbits, euglycemic hyperinsulinemic clamp studies in rats and subchronic studies in manifestly diabetic KK-AY mice. Extrapancreatic activity of sulfonylureas as deduced from the ranking in vivo between glimepiride and glibenclamide directly on peripheral tissues would imply a similar ranking between the two drugs in glucose utilizing processes in isolated muscle and fat cells. Indeed, glimepiride exhibits a higher potency compared to glibenclamide with respect to stimulation of glucose transport, glucose transporter isoform 4 (GLUT4) translocation and lipid and glycogen synthesis in normal and insulin-resistant adipocytes and in muscle cells, as well as of the potential underlying signalling processes examined at the molecular level. The molecular basis for the sulfonylurea-induced increase of glucose transport and non-oxidative glucose metabolism may rely on the dephosphorylation of key metabolic proteins/enzymes, like GLUT4 as demonstrated in isolated rat adipocytes. Activation of certain serine/threonine-specific protein phosphatases by insulin has been postulated to be mediated by the mitogen-activated protein kinase (MAPK) pathway and phosphatidylinositol (P1)-3'-kinase. However, there was no evidence that these pathways are involved in the regulation of protein phosphatase activity by sulfonylureas. Binding and photoaffinity studies showed that glimepiride associates in a time- and concentration dependent non-saturable manner with detergent-insoluble complexes of the plasma membrane which may correspond to caveolae. This association seems to be based on the interaction of glimepiride with glycosyl-phosphatidylinositol (GPI) lipids and membrane protein anchors. These were found to be enriched in detergent-insoluble complexes together with a GPI-specific phospholipase (PLC), the caveolae-specific coast protein, caveolin, and acylated tyrosine kinases of the src family. Sulfonylureas were found to stimulate the GPI-PLC and tyrosine phosphorylation of caveolin. This is presumably caused by direct interaction of the sulfonylurea into caveolar glycolipids and stimulation of a caveolar src tyrosine kinase, respectively. In accordance with the higher potency of glimepiride in vivo and in glucose transport/metabolism in vitro, the EC50 values for GPI-PLC activation and caveolin phosphorylation were lower for glimepiride than those for glibenclamide. The stimulation of protein tyrosine phosphorylation by sulfonylureas via this pathway not involving the insulin signaling cascade may be coupled to activation of specific protein phosphatases regulating glucose transport and metabolism. The concentrations required in vitro were higher than the reported therapeutic plasma concentrations. However, provided that the observed time-dependent accumulation of glimepiride in caveolae of peripheral cells were of functional relevance for stimulation of glucose transport/metabolism and would also occur in vivo, due to the longer exposure times even at lower drug concentrations the insulin-independent blood glucose decreasing activity of sulfonylureas might become effective in vivo.
Article
An international, prospective, double-blind trial compared the long-term therapeutic value of glimepiride with glibenclamide in patients with Type 2 diabetes mellitus. Patients stabilised on glibenclamide were randomised to 1 mg glimepiride (524 patients) or 2.5 mg glibenclamide (520 patients). The treatment groups were comparable at baseline with respect to age (60.2 years), body mass index (26.5 kg/m2), duration of diabetes (5.0 years) and fasting blood glucose levels (163 mg/dl [9.0 mmol/l]). Doses were increased stepwise, up to 8 mg for glimepiride (once-daily) and 20 mg for glibenclamide (> 10 mg as divided dose), until metabolic control (fasting blood glucose < or = 150 mg/dl [8.3 mmol/l]), or maximum dose was achieved. After one year of treatment, patients entered a long-term follow-up study. Primary endpoints for evaluation of metabolic control, mean glycated haemoglobin and mean fasting blood glucose, were 8.4% and 174 mg/dl (9.7 mmol/l) for glimepiride and 8.3% and 168 mg/dl (9.3 mmol/l) for glibenclamide. Differences between treatment groups were not considered clinically relevant (95% confidence intervals (-0.05, 0.19%) for glycated haemoglobin and (2, 11 mg/dl) [0.1, 0.6 mmol/l] for fasting blood glucose). Statistically significant lower fasting insulin and C-peptide values were observed in glimepiride patients compared with glibenclamide (differences: insulin, -0.92 microU/ml [p = 0.04]; C-peptide, -0.14 ng/ml [p = 0.03]). Both treatment groups showed an equivalent safety profile. Adverse events were consistent with the nature of the diabetic patient population studied. Fewer hypoglycaemic reactions occurred with glimepiride than with glibenclamide (105 versus 150 episodes). The long-term follow-up (457 patients) confirmed that glimepiride (1-8 mg) once daily provides equivalent metabolic control to a higher dosage (2.5-20.0 mg) of glibenclamide. Both treatments were well tolerated.
Article
To investigate the metabolic effects and frequency of adverse events with 6 mg of glimepiride, a new oral sulfonylurea, given both in once- and twice-daily dosages to patients with non-insulin-dependent diabetes mellitus (NIDDM). This 15-week study involved 161 subjects with NIDDM. Subjects were randomized into two groups. For 4 weeks, group 1 received glimepiride 3 mg twice daily, and group 2 received glimepiride 6 mg once daily. After a 3-week placebo-washout period, twice- and once-daily regimens were crossed over for a second 4-week treatment period. Subjects were hospitalized at the end of each placebo or active-treatment phase. Their glucose concentrations were recorded at 20 time points over a 24-hour period, and their insulin and C-peptide concentrations were recorded at 16 time points over the same period. Parameters that were calculated included fasting, 24-hour, and postprandial concentrations of glucose, insulin, and C-peptide. One hundred six patients were randomized to receive treatment; 94 completed the entire study. Existing physiologic mechanisms of glucose control were apparently unimpaired by glimepiride treatment. Insulin concentrations increased more during the postprandial glucose peaks than when subjects were fasting. Both twice- and once-daily regimens proved equally effective in reducing concentrations of fasting, postbreakfast, postlunch, and postdinner plasma glucose. Twenty-four-hour mean glucose concentrations showed a slightly greater decrease from baseline for the twice-daily regimen; the difference between the regimens was statistically significant but not clinically meaningful. The incidence of adverse events with glimepiride approximated that obtained with placebo, with both groups reporting only one adverse event, headache, in more than 5% of the subjects. Glimepiride is equally effective whether administered once or twice daily. Glimepiride seems to stimulate insulin production primarily after meals, when plasma glucose concentrations are highest, but controls blood glucose throughout the day.
Twelve healthy fasting male volunteers received a single 1.0 mg dose of glimepiride either as an intravenous injection over one minute or as a tablet. Blood and urine samples were taken before drug administration and afterwards for up to 24 hours (blood) and 48 hours (urine) to determine serum and urinary concentrations of glimepiride and its hydroxy- and carboxy-metabolites (M1 and M2). There were no statistically significant differences between mean serum pharmacokinetic parameters for the oral and intravenous formulations either with glimepiride or M1. Mean urinary recovery of M1 plus M2 was 50% of the dose for the glimepiride tablet and 51% for the intravenous injection. The absolute bioavailability of the tablet formulation was 107% (AUDC(glimepiride)), 109% (AUDC(M1)) and 97% (urinary recovery). The tablet formulation of glimepiride is completely bioavailable and was safe and well tolerated in healthy volunteers.