Computer-Assisted Optimization of Liquid Chromatography Separations of Drugs and Related Substances

Abstract

Nowadays, liquid chromatography (LC) has an established place among other analytical techniques. This separation technique is commonly used in pharmaceutical laboratories. LC method optimization is usually realized by a trialand-error method based on the knowledge of the chromatographic process. Therefore, LC method development is often time-consuming and involves intensive exploitation of equipment and a substantial consumption of chemicals. Over the last few years, the progress in computer program development has assisted chromatographers in method development also. The rational selection of optimized experimental conditions for the chromatographic separation of analytes can also be realized nowadays by means of specialized algorithms (especially applying those used in the commercially available DryLab and ChromSword software). The aim of the study is to present recent achievements associated with the optimization of chromatographic separations of drugs and related compounds realized in reversed-phase liquid chromatography (RP-LC) systems. Considering applications in pharmaceutical analysis, several examples are provided. Optimization based just on experimental chromatographic measurements and additionally employing the quantitative structure-retention relationships (QSRR) is discussed in view of the opportunity to obtain practically useful separation information.

Application of Multidimensional Screening and Analysis and Computer Simulation Software for Rapid HPLC Method Development

“…Ammonium acetate buffer (100 mM, pH 5.0) was prepared by dissolving 3.85 g of NH 4 OAc in 500 mL of water and adjusting the pH to 5.0 with diluted acetic acid glacial. Potassium dihydrogen phosphate buffer (100 mM) was prepared by dissolving 6.86 g of KH 2 PO 4 into 500 mL of water.…”

“…The determined optimum is in many cases not the "global optimum" [3]. Process understanding at the early and late development stages has been greatly enhanced by the use of fully automated method development using column selection systems and computer simulation software [4][5][6][7][8][9][10][11][12][13][14][15]. The objective of the automated method development is to provide experimental decision outcomes relevant to the optimization of complex separations as well as the control of the instrumentation, column selection, mobile phase choice, and other experimental parameters.…”

“…The objective of the automated method development is to provide experimental decision outcomes relevant to the optimization of complex separations as well as the control of the instrumentation, column selection, mobile phase choice, and other experimental parameters. The progress in computer software applications for method development was recently reviewed by Bączek and Tomasz [4]. Computer simulation programs based on experimental chromatographic measurements include Drylab ® (Molnar-Institut für angewandte chromatographie, Berlin, Germany) and Chromsword (Dr. Galushko Software Entwicklung GmbH, Muehltal, Germany) [4][5][6][7][8][9][10][11][12]14,15].…”

“…The progress in computer software applications for method development was recently reviewed by Bączek and Tomasz [4]. Computer simulation programs based on experimental chromatographic measurements include Drylab ® (Molnar-Institut für angewandte chromatographie, Berlin, Germany) and Chromsword (Dr. Galushko Software Entwicklung GmbH, Muehltal, Germany) [4][5][6][7][8][9][10][11][12]14,15]. Other software products such as Fusion AE use design of experiments to generate appropriate retention models to predict the most favorable chromatographic conditions [13].…”

Optimization of Thin-layer Chromatography and High-Performance Liquid Chromatographic Method for Piper guineense Extracts

“…DryLab and other computer simulation programs have provided rapid and optimal HPLC conditions for the separation of analytes, drugs and other pharmaceutical formulations [16]. The analysis, characterization and structural elucidation of bioactive compounds from plant extracts is a difficult task to accomplish, due to the presence of numerous compounds.…”