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Chamseddin C.,University of Greifswald | Molnar I.,Molnar Institute for Applied Chromatography | Jira T.,University of Greifswald
Journal of Chromatography A | Year: 2013

The recently dramatic increase in the available choices of reversed-phase columns could be an advantage of this mode of separation. However, due to the insufficiency of available information in terms of the exact functionality of these phases and the similarities and differences between these newly introduced and conventional reversed-phase columns, it is now somehow problematic to determine which could be the best column for a given analytical problem. There is no single column that will give us a good separation for all applications. As a result, there have been several attempts to develop testing strategies to characterize column chemistries. In this study three of the most widely used and acceptable approaches for the characterization of reversed-phase columns, which are Tanaka, United States Pharmacopeia (USP), and Snyder-Dolan, are systemically applied to investigate the chromatographic properties of calixarene- and resorcinarene-bonded stationary phases, polar-embedded and polar-endcapped stationary phases, phenyl and ether-linked phenyl with the presence of conventional alkyl-bonded phases (octyl- and octadecylsilane). Although all column classification systems aim to evaluate "more or less" the same characteristics, each system uses different test mixtures in different chromatographic conditions. It is therefore very important to evaluate the similarities and differences in the resulted "column parameters" and the possible interchangeability of them. The results of this comparative study show that the used parameters of Tanaka and of Snyder-Dolan have in many cases a good to very good correlation. The USP approach, which is based on single run, is related to Tanaka and Snyder-Dolan only in terms of hydrophobic characters, and no relation could establish in the other parameters. The hydrophobic-subtraction model could be extended to describe the ligand-solute interactions of calixarene- and resorcinarene-bonded stationary phases, which are belonging to reversed phase material. However they show, depending on the analytes, some additional interactions, since their steric, polar and ionic properties are different compared to those of conventional alkyl-bonded phases. © 2013 Elsevier B.V.


Racz N.,Budapest University of Technology and Economics | Kormany R.,EGIS Pharmaceuticals Plc. | Fekete J.,Budapest University of Technology and Economics | Molnar I.,Molnar Institute for Applied Chromatography
Journal of Pharmaceutical and Biomedical Analysis | Year: 2015

Column technology needs further improvement even today. To get information of batch-to-batch repeatability, intelligent modeling software was applied. Twelve columns from the same production process, but from different batches were compared in this work. In this paper, the retention parameters of these columns with real life sample solutes were studied. The following parameters were selected for measurements: gradient time, temperature and pH. Based on calculated results, batch-to-batch repeatability of BEH columns was evaluated. Two parallel measurements on two columns from the same batch were performed to obtain information about the quality of packing. Calculating the average of individual working points at the highest critical resolution (Rs,crit) it was found that the robustness, calculated with a newly released robustness module, had a success rate >98% among the predicted 36=729 experiments for all 12 columns. With the help of retention modeling all substances could be separated independently from the batch and/or packing, using the same conditions, having high robustness of the experiments. © 2015 Elsevier B.V.


Kormany R.,EGIS Pharmaceuticals Plc. | Molnar I.,Molnar Institute for Applied Chromatography | Fekete J.,Budapest University of Technology and Economics | Guillarme D.,University of Geneva | Fekete S.,University of Geneva
Chromatographia | Year: 2014

This paper describes a new and fast ultra-high pressure liquid chromatographic separation of amlodipine and bisoprolol and all their closely related compounds, for impurity profiling purposes. Computer-assisted method development was applied and the impact of several state-of-the-art stationary phase column chemistries (50 x 2.1 mm, sub-2 μm, and core-shell type materials) on the achievable selectivity and resolution was investigated. The work was performed according to quality by design principles using design of experiment with three experimental factors; namely the gradient time (t G), temperature (T), and mobile phase pH. Thanks to modeling software, it was proved that the separation of all compounds was feasible on numerous column chemistries within <10 min, by proper adjustments of variables. It was also demonstrated that the reliability of predictions was good, as the predicted retention times and resolutions were in good agreement with the experimental ones. The final, optimized method separates 16 peaks related to amlodipine and bisoprolol within 7 min, ensuring baseline resolution between all peak-pairs. © 2014 Springer-Verlag.


Hanafi R.,German University in Cairo | Spahn-Langguth H.,German University in Cairo | Mahran L.,German University in Cairo | Heikal O.,German University in Cairo | And 6 more authors.
Chromatographia | Year: 2012

Following administration of the acidic drug tolmetin (TOL) anaphylactic reactions occurred, which have been hypothesized to be related to the formation of reactive acyl glucuronides. Recently, glutathione adducts have been detected upon incubation of TOL with human liver microsomal preparations, which proved that oxidative activation might also be a pathway of formation of reactive\- possibly toxic\-glutathione metabolites of TOL. The aim of this work was to develop a new and robust HPLC method to investigate the in vivo effect of 2 coadministered drugs/nutritional supplements on the kinetics of TOL in rats (cimetidine; CIM) known to be a potent inhibitor of CYP3A4, an enzyme that catalyzes the oxidative metabolism and Quercetin; and QUE which induces UGT1A6, an enzyme involved in glucuronidation of acidic drugs. DryLab®, a computer simulation software package, was used to assist in the development and optimization of the HPLC method used for separation of TOL and the two potential kinetic modulators together with three potential internal standards (zomepirac, carvedilol and fexofenadine). The method was validated in biological samples obtained from rats. Non-compartmental pharmacokinetic analysis of data obtained from plasma and rat liver tissue showed significantly higher concentrations of TOL in the presence of CIM; and significantly longer elimination halflife lives in presence of QUE, which implies that drugs or food components interacting with CYP3A4 cause alteration in the metabolic oxidative biotransformation of TOL in vivo leading to accumulation of TOL in the body through a decrease of its clearance. These findings might account for to the side-effects associated with TOL when co-administered with such kinetic modulators. © 2012 Springer-Verlag.


Molnar I.,Molnar Institute for Applied Chromatography | Monks K.E.,Molnar Institute for Applied Chromatography
Chromatographia | Year: 2011

The present paper starts by taking a look back at some of the pioneering work in high pressure liquid chromatography (HPLC) that went on in Csaba Horváth's laboratory in 1970s, through the eyes of I. Molnár. It then goes on to describe a very modern approach to HPLC method development within the Quality by Design framework: the multifactorial optimization of three critical HPLC method parameters, i.e. gradient time (t G), temperature (T), and ternary composition (B1:B2) based on 12 experiments. The effect of these experimental variables on critical resolution and selectivity was carried out in such a way as to systematically vary all three factors simultaneously. © 2011 Springer-Verlag.

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