Micellar Thin Layer Chromatography and Computer-Aided Analysis of Empagliflozin, Linagliptin and Metformin HCl Ternary Mixture.

The present work was performed in order to study the mechanism of micellar thin layer chromatography (MTLC) and to develop a new simple and sensitive simultaneous MTLC method for separation of empagliflozin, Linagliptin and metformin hydrochloride ternary mixture. The study was done using three different surfactants; sodium dodecyl sulphate (SDS), benzalkonium chloride (BAC) and polysorbate 80 (tween 80). Chromatographic procedure was performed using micellar mobile phase that composed of aqueous solution of each surfactant and methanol (6: 4 v/v) and micellar TLC determination at λmax 237 nm. Separation using SDS (anionic surfactant) and BAC (cationic surfactant) depends on ionization potential (AMI-IP), partition coefficient (logP (o/w)) and hydrogen bond donor atoms (a-don), whereas separation using tween 80 depends mainly on the lipophilicity (RM0), solvation energy (E-sol) and Van der Waals energy (E-vdw). Quantitative structure-retention relationships study was carried out, modeled, evaluated and validated using molecular operating environment software.

Simple TLC-spectrodensitometric method for studying lipophilicity and quantitative analysis of hypoglycemic drugs in their binary mixture.

A selective and simple salting-out-assisted thin-layer chromatographic methodology was developed for the simultaneous determination of two oral hypoglycemic drugs, dapagliflozin (DAPA) and metformin (MET) in their pure forms, tablets and spiked human plasma samples. Silica gel 60 F254 plates were used in the separation of the two drugs using a mobile phase consisting of 0.5 m (NH4 )2 SO4 and methanol (3:7, v/v). The plates were scanned in the reflectance mode at λmax = 237 nm. The obtained retardation factor (Rf ) values for DAPA and MET were 0.77 ± 0.02 and 0.25 ± 0.02, respectively. The thin-layer chromatography method was validated according to International Conference on Harmonization guidelines. The peak areas were linearly increased with the increases in concentrations of 45-1,000 and 50-1,500 ng/band for DAPA and MET, respectively. Moreover, the method was applied to estimate the molecular lipophilicity parameters of DAPA and MET via retention data. The suggested method was efficiently utilized for the analysis of DAPA and MET in pharmaceutical tablets and plasma samples with recoveries 98.4-100.4 and RSDs in the ranges of 1.4-2.6 and 2.2-3.0% for DAPA and MET, respectively.

An efficient hydrophilic interaction liquid chromatographic method for the simultaneous determination of metformin and pioglitazone using high-purity silica column.

Hydrophilic interaction liquid chromatography (HILIC) provides a feasible approach to effectively separate polar compounds in complex matrices. Herein, a simple, reproducible and efficient HILIC method was developed for the simultaneous determination of pioglitazone. HCl (PIO) and metformin HCl (MET) in rabbit plasma. High-purity silica column was used for rapid and efficient separation of these co-administered drugs. The chromatographic parameters were optimized for best separation. The proposed HILIC system provides high separation efficiency with good peak shape compared to reversed phase (RP) chromatography. Additionally, a simple isocratic elution mode with a mobile phase composed of a mixture of methanol and 10mM phosphate buffer (pH 3.0) (94:6, v/v) was used and the effluent was monitored at 230nm. The method was validated in accordance with the requirements of US-FDA guidelines and was found to behave efficiently for the intended purpose. The correlation coefficient of 0.9992 was obtained in the concentration ranges of 0.5-100µgmL(-1). The limits of detection (S/N=3) and quantification (S/N=10) were 0.16 and 0.5ngmL(-1), respectively. The retention times were 3.4 and 5.0min for PIO and MET, respectively. Plasma levels were successfully determined in rabbit with satisfactory precision and accuracy. In addition, the stability tests in rabbit plasma proved reliable stability under the experimental conditions. The developed HILIC method was applied successfully to study the pharmacokinetic behaviors of the studied analytes in rabbit plasma after a single oral dose containing PIO and MET.

New Salting Out Stability-Indicating and Kinetic Thin Layer Chromatographic Method for Determination of Glimepiride and Metformin HCl Binary Mixture.

A simple, selective salting out and stability-indicating thin layer chromatographic (SOTLC) technique was developed for determination of two antidiabetic drugs; glimepiride and metformin HCl in pure and in tablets as a binary mixture. Separation was performed on silica gel 60 F254 plates using aqueous ammonium sulfate and acetonitrile (7:3, v/v) as a mobile phase. The Rf values were 0.26 ± 0.02 and 0.73 ± 0.02 for glimepiride and metformin HCl, respectively. The separated bands were scanned at λ 237 nm using CAMAG TLC scanner III. The proposed method focusing on study of all the factors that play important role in the mechanism of salting out process. The proposed method was validated according to ICH guidelines and complied with USP31-NF26 validation guidelines. The correlation coefficients of calibration curves were 0.996 and 0.997 for glimepiride and metformin HCl, respectively, in the concentration range of 60-1,400 ng/band for both drugs. The investigated drugs were also subjected to acidic, basic, oxidative and photo-degradation and kinetic study was carried out.

Salting-out thin-layer chromatography and computational analysis of some oral hypoglycemic drugs.

A quantitative structure-retention relationship study of some oral hypoglycemic drugs was carried out using a salting-out thin-layer chromatographic technique. Aqueous solution of ammonium sulfate and acetonitrile was used as a mobile phase. It was established that the applied mobile phase has different effects on retention of the studied oral antidiabetic drugs. The factors that affect the salting-out process were determined. In this study a good correlation between the structures of the investigated drugs with the retention data and molecular descriptors was established throughout computational analysis and using molecular operating environment software, focusing on octanol/water partition coefficient, molar refractivity, total hydrophobic surface area, hydrophobic volume, Van der Waals energy and solvation energy. Quantitative structure-retention relationship modeling for the separation of the investigated drugs was carried out, validated and evaluated.