Glimepiride In Plasma Research Articles

Simultaneous Determination of Atorvastatin and Glimepiride by LC-MS/MS in Human Plasma and Its Application to a Pharmacokinetic Study

The aim of the proposed research work was to develop and validate a simple, selective high sensitive and high-throughput assay for the simultaneous estimation of Atorvastatin and Glimepiride in human plasma using liquid chromatography tandem mass spectrometry (LC-MS/MS). Atorvastatin–Glimepiride combines a competitive inhibitor of HMG-CoA reductase and a sulfonylurea anti-diabetic drug. The purpose of this study was to develop single method for Atorvastatin and Glimepiride in plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS) that would result into a simultaneous estimation of Atorvastatin and Glimepiride avoiding acid –lactone inter conversions right from sample collections to analysis on the LC-MS/MS. Sample collection procedure optimized for Atorvastatin holds good for Glimepiride, hence resulting into a simultaneous estimation of Atorvastatin and Glimepiride. Liquid-liquid extraction and liquid chromatography coupled to positive ion mode tandem mass spectrometry was used to develop the method and was validated according to US FDA guidelines. The calibration curves for two analytes were linear (R2 ≥ 0.9950, n = 4) over the concentration range of 0.2 - 30 ng/mL for Atorvastatin and 1 - 250 ng/mL for Glimepiride. Mean extraction recoveries 80.34 ± 9.43 for Atorvastatin and 88.19 ± 7.13 for Glimepiride. Intra- and inter-run mean percent accuracy was between 85% - 115% and percent imprecision was ≤15%. Stability studies revealed that Atorvastatin and Glimepiride were stable in plasma during bench top (10.5 h at room temperature), in Injector (47.5 h), at the end of three successive freeze and thaw cycles and long term at -65℃ ± 15℃ for 114 days. The method was successfully applied to the study of pharmacokinetics of Atorvastatin and Glimepiride in healthy volunteers. Simultaneous estimation of Atorvastatin and Glimepiride is cost effective, reduces analysis cycle time, enables effective utilization of resources and reduces bleeding burden on human volunteers.

Multi‐objective optimization strategy based on desirability functions used for electrophoratic separation and quantification of rosiglitazone and glimepiride in plasma and formulations

Multiple response simultaneous optimization employing Derringer's desirability function was used for the development of a capillary electrophoresis method for the simultaneous determination of rosiglitazone (RSG) and glimepiride (GLM) in plasma and formulations. Twenty experiments, taking the two resolutions, the analysis time, and the capillary current as the responses with three important factors--buffer morality, volte and column temperature--were used to design mathematical models. The experimental responses were fitted into a second order polynomial and the six responses were simultaneously optimized to predict the optimum conditions for the effective separation of the studied compounds. The separation was carried out by using capillary zone electrophoresis (CZE) with a silica capillary column and diode array detector at 210 nm. The optimum assay conditions were 52 mmol l⁻¹ phosphate buffer, pH 7, and voltage of 22 kV at 29 °C. The method showed good agreement between the experimental data and predictive value throughout the studied parameter space. The assay limit of detection was 0.02 µg ml⁻¹ and the effective working range at relative standard deviation (RSD) of ≤ 5% was 0.05-16 µg ml⁻¹ (r = 0.999) for both drugs. Analytical recoveries of the studied drugs from spiked plasma were 97.2-101.9 ± 0.31-3.0%. The precision of the assay was satisfactory; RSD was 1.07 and 1.14 for intra- and inter-assay precision, respectively. The proposed method has a great value in routine analysis of RSG and GLM for its therapeutic monitoring and pharmacokinetic studies.