Computer-Assisted Method Development

Procedures used vary from trial-and-error methods to more sophisticated approaches including the window diagram, the simplex method, the PRISMA method, chemometric method, or computer-assisted methods. Many of these procedures were originally developed for HPLC and were apphed to TLC with appropriate changes in methodology. In the majority of the procedures, a set of solvents is selected as components of the mobile phase and one of the mentioned procedures is then used to optimize their relative proportions. Chemometric methods make possible to choose the minimum number of chromatographic systems needed to perform the best separation. 

Molnar, I. Validation of robust chromatography methods using computer-assisted method development for quahty control. LC GC Int. 1996, 9 (12), 800-808. 

Nonequilibrium, or film, methods provide physically realistic formulations of the problem that yield more accurate local coefficients at the expense of complexity. Colburn and Hougen [77] developed a trial-and-error solution procedure for condensation of a single vapor mixed with a noncondensable gas. Colburn and Drew [203] extended the method to include condensation of binary vapor mixtures (with no noncondensables). Price and Bell [204] showed how to use the Colburn and Drew [203] method in computer-assisted design. 

Glajch, J.L., Snyder, L.R., editors (1990). Computer-Assisted Method Development for High-Performance Liquid Chromatography. Elsevier, Amsterdam. 

This derivation shows that retention time is dependant on three factors temperature, energies of intermolecular interactions and flow rate. Temperature and flow rate are controlled by the user. Energies of intermolecular interactions are controlled by stationary phase choice. This theory is also the basis for the popular software programs that are available for computer-assisted method development and optimization [4,5,6,7]. More detailed descriptions of the theory behind retention times can be found in the appropriate chapters in the texts listed in the bibliography. 

L. van Heukelem and C.S. Thomas, Computer assisted high-performance liquid chromatography method development with applications to the isolation and analysis of phytoplankton pigments. J. Chromatogr.A 910 (2001) 31—49. 

A number of computer software packages are available to the analyst to assist in the planning and execution of both method development and validation experiments. The attraction of these systems is that they can automate the validation process from planning the experiment to test execution to the presentation of the data in a final report form. 

The goal of ECAT is to provide assistance to the user of a chromatograph in the development of an HPLC method. To do this, one must specify the tasks performed in developing an analytical method. The computer performs these tasks by processing information. In ECAT we are calling the collection of information specific to a task a Module. The modules and information flow which will be needed for the completely implemented ECAT are shown in Figure 2. 

As computers become more pervasive and increasingly powerful, specialized programs and databases are being developed to assist in a wide variety of research efforts. This is true in the search for solvent alternatives, and in this section we review the application of computers to solvent substitution studies and cover computer-aided molecular design of new solvents, methods developed for the prediction of physical properties, methods for predicting less precise chemical characteristics such as toxicity and carcinogenicity, and computer-aided design of alternative synthetic pathways. 

Investigative toxicology Determine sequence and mechanisms of toxic action. Discover the genes, proteins, pathways involved. Develop new methods for assessing toxicity use computer-assisted modeling. 

Liquid chromatography is now a mature technique. Instruments are reliable and increasingly computer assisted. Column-to-column reproducibility is ensured by most manufacturers. The quest for the universal detector is about to end with the advent of a sophisticated and miniaturized MS detector. Development of a method can be achieved in a rather short period with available software. The emphasis is on validation more than on how to handle it. Capillary columns are sure to improve, and the trend will be toward many parallel analyses. 

N. G. Mellish, Computer-assisted HPLC method development in a pharmaceutical laboratory, LC-GC, 9 845 (1990). 

They generally lack sensitivity and a direct relation to molecular structure. GC-MS is fast, direct, and very sensitive, and the spectrum provides a result which puts identification beyond dispute. Computer-assisted systems are now available which embody extensive drug reference libraries and can be automatically searched to identify unknown spectra. The further development of chemical ionization and mass fragmentography methods using stable isotopes now permits very accurate quantitative work. 

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