Optimization strategies in chiral liquid chromatography

The advent of new LC column technology for the separation of chiral drugs and metabolites has transformed the practice of enantiomer separation for the quality control of chiral drugs and for biological studies on chiral entities. The wide variety of separation principles now exploited for chiral analysis has led to the development of more than 40 different columns, plus the complementary technology where a chiral mobile phase additive is used with a regular reversed-phase column. The multiplicity of choice for chiral separations can present major difficulties in selecting a suitable starting point for a particular enantiomer separation. However, for a particular chiral modality, the problem is then to rapidly assess its suitability for a given analyte, and then the optimize the enantiomeric resolution observed. These objectives can be achieved by using a combination of systematic optimization strategies, together with diagnostic tests for peak resolution and homogeneity. Thus factorial design (Berridge 1985) can be used to assess the practical range and extent of interaction of those eluent parameters that determine chiral resolution. This can then be followed by computer-aided sequential simplex optimization to establish the conditions for the best available resolution on the specific chiral system selected (Fell et al . 1989). The central composite (factorial) design requires 1) experiments for k factors, and permits a second-order polynomial to be fitted to the data, with the advantage that the model so developed can be used predictively (Berridge 1985). Simplex lattice design is a form of simultaneous optimization design based on isoeluotropic mixtures of mobile phase to generate data that allow a linear model to be developed for predictive purposes (Schoenmakers 1986).

2013 ◽  
Vol 3 (1) ◽  
pp. 6 ◽  
Author(s):  
Mariarita Laforgia ◽  
Anna Elisa Quatrale ◽  
Nicola A. Colabufo ◽  
Amalia Azzariti ◽  
Angelo Paradiso ◽  
...  

Several clinically used anticancer drugs are well-known as far as their pharmacologic properties are concerned, but scarcely ever the interest towards their physico-chemical characteristics in solution led to practical acknowledgement in their management. Thanks to the Units for Centralized Anticancer Drug Handling, the importance to evaluate the concentration of saturation (physical stability) or the possible transformations undergone by a drug in solution (chemical stability) has become the starting point for avoiding useless wasting drugs and economic resources. By HPLC experiments we have demonstrated that the solutions of two drugs, docetaxel and irinotecan, are particularly stable at different concentrations and times of analyses in our experimental conditions. The best mobile phase for docetaxel was water/methanol/acetonitrile in 42/32/26 volumetric ratio: for halving concentrations (0.72-0.36-0.18-0.09 mg/mL) in NaCl 0.9%, the highest value gave a six-day and the three lower concentrations a fourteen-day stability, when storage occurred at room temperature and light protected. Elution of irinotecan was possible through an analysis in mobile phase gradient: at t0 a 20% ammonium acetate 10 mM and 80% methanol mixture, and after 5 min, a 80% ammonium acetate 10 mM and 20% methanol mixture. The physico-chemical stability was showed for five days, for any concentration of analysis when storage occurred at 2-8°C and light protected.


2017 ◽  
Vol 15 (1) ◽  
pp. 293-298
Author(s):  
Pakinaz Y. Khashaba ◽  
Hassan Refat H. Ali ◽  
Mohamed M. El-Wekil

AbstractA simple, rapid, cost-effective, and sensitive TLC-spectrodensitometric method for simultaneous determination of esomeprazole and domperidone was developed and tested in human plasma. Ethyl acetate: methanol: benzene: acetonitrile (5: 4: 8: 3, v/v/v/v) mobile phase was used for separation on TLC plates detected at 286 nm. The linearity ranges were 5-1200 and 2-600 ng/ spot for esomeprazole and domperidone, and limits of detection were 1.73 and 0.59 ng/spot. The effects of four variables affecting Rf were evaluated by fractional factorial design. The benzene volume and saturation time had significant effects.


2012 ◽  
Vol 2 (2) ◽  
pp. 45-68
Author(s):  
Moussa Diaf ◽  
Kamal Hammouche ◽  
Patrick Siarry

Biological studies highlighting the collective behavior of ants in fulfilling various tasks by using their complex indirect communication process have constituted the starting point for many physical systems and various ant colony algorithms. Each ant colony is considered as a superorganism which operates as a unified entity made up of simple agents. These agents (ants) interact locally with one another and with their environment, particularly in finding the shortest path from the nest to food sources without any centralized control dictating the behavior of individual agents. It is this coordination mechanism that has inspired researchers to develop plenty of metaheuristic algorithms in order to find good solutions for NP-hard combinatorial optimization problems. In this article, the authors give a biological description of these fascinating insects and their complex indirect communication process. From this rich source of inspiration for researchers, the authors show how, through the real ant, artificial ant is modeled and applied in combinatorial optimization, data clustering, collective robotics, and image processing.


Chirality ◽  
2004 ◽  
Vol 16 (8) ◽  
pp. 493-498 ◽  
Author(s):  
Rodger W. Stringham ◽  
Kenneth G. Lynam ◽  
Barbara S. Lord

2019 ◽  
Vol 10 (1) ◽  
pp. 10-22
Author(s):  
Shantanu Shankar Bagchi

In the context of the hotel industry, one of the biggest and capital-intensive challenges a decision maker has is to decide on the capacity of the hotel. While taking this decision, the decision maker needs to take seasonality of demand into consideration. Also, the interplay between price and demand also play a major role on this decision. In this study, an effort is made to simultaneously identify the optimal capacity and pricing policy of a hotel in the presence of a stochastic demand environment. Differential calculus is used to identify the solution. Both capacity and price are considered as decision variables for the decision maker. To comply with reality, the seasonality in demand is incorporated in the form of bi-level demand. Numerical illustrations are also shown to explain the decision-making process. This study offers a starting point for an entrepreneur to decide both capacity and pricing for their upcoming hotel.


2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Hua He ◽  
Lien Ai Pham-Huy ◽  
Pierre Dramou ◽  
Deli Xiao ◽  
Pengli Zuo ◽  
...  

Carbon nanotubes (CNTs) are allotropes of carbon, made of graphite and constructed in cylindrical tubes with nanometer in diameter and several millimeters in length. Their impressive structural, mechanical, and electronic properties are due to their small size and mass, their strong mechanical potency, and their high electrical and thermal conductivity. CNTs have been successfully applied in pharmacy and medicine due to their high surface area that is capable of adsorbing or conjugating with a wide variety of therapeutic and diagnostic agents (drugs, genes, vaccines, antibodies, biosensors, etc.). They have been first proven to be an excellent vehicle for drug delivery directly into cells without metabolism by the body. Then other applications of CNTs have been extensively performed not only for drug and gene therapies but also for tissue regeneration, biosensor diagnosis, enantiomer separation of chiral drugs, extraction and analysis of drugs and pollutants. Moreover, CNTs have been recently revealed as a promising antioxidant. This minireview focuses the applications of CNTs in all fields of pharmacy and medicine from therapeutics to analysis and diagnosis as cited above. It also examines the pharmacokinetics, metabolism and toxicity of different forms of CNTs and discusses the perspectives, the advantages and the obstacles of this promising bionanotechnology in the future.


2018 ◽  
Vol 25 (33) ◽  
pp. 4152-4188 ◽  
Author(s):  
Mehmet Gumustas ◽  
Sibel A. Ozkan ◽  
Bezhan Chankvetadze

While the amino acids, enzymes and hormones are chiral, chirality plays significant role in the life of plants, animals, as well as the human being. Chirality of molecules is important in various industries, such as pharmaceutical, agricultural, food, electronics, etc. Chiral drugs may have different bioavailability, distribution, biotransformation and excretion, as well as quantitatively and/or qualitatively different pharmacological or toxic properties. Enantiomerically pure chiral drugs have been increasingly developed for the pharmaceutical market due to their superiority from the viewpoints of potency and safety. This is supported by the development of new methods for enantioselective production of the chiral compounds, as well as by the capability of the enantioselective analytical methods to allow a detection and quantification of minor enantiomeric impurity in the presence of another enantiomer in a large excess. The aim of the present review is to provide a short summary of the basic principles of chiral separations on an analytical and preparative scale. In addition, some selected applications for analytical techniques, such as gas chromatography, supercritical fluid chromatography, high performance liquid chromatography, capillary electrophoresis and capillary electrochromatography for the separation of enantiomers of chiral pharmaceuticals published in the last two years are also discussed.


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