Automated Methods Development

Method development can be a time-consuming process and requires quite a substantial amount of guesswork. Hundreds of columns are available, with 

POPLC Bischoff Chromatography 32 Karat Software Beckman Turbo Method Development Perkin Elmer ILS ChromSmart MD Agilent 

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QuanOptimize from Micromass also allows automated method development for quantitative LC/MS/MS. It automatically identifies the best method for each compound, then runs batches of samples for quantitative analyses and report results in a QuanLynx browser. Thermo recently launched a similar product for automatic MS tuning. Known as QuickQuan, it generates data and stores it in a central Microsoft Access or Oracle database for future access. The infusion-based valve switching auto-tuning device allows individual compounds to be fully and automatically optimized in about 1 min. 

Rozenman, Y. and Di Bussolo, J. M., Developing Robust HPLC Separations Using an Automated Method Development System, Pharm. Tech., 10-19, 1998. 

A word of warning if you are planning to do automated methods development. The HPLC system you buy will generally dictate the type of methods development software that is available to you this is not an add-on procedure that you can purchase at a later time, except from the manufacturer of your system computer. If you are contemplating a need for this technique, I would recommend strongly that you talk to other people who are already successfully doing this type of work and find out their HPLC system source and buy from the same place. 

Autoinjector—An injection device for automated methods development in which the sample loop is repeatedly filled from a large sample reservoir rather than a sample vial carousel. 

Step 6 Screen Different Columns/Mobile Phases Using an Automated Method Development System or Column Switcher. If the desired selectivity is not obtained or the peak is not spectrally homogeneous from Step 5, then different columns (two to six) and mobile phases can be screened using a column switcher. The typical mobile phases that could be screened include acetonitrile, methanol, and acetonitrile/methanol mixtures using the same "pH... 

Recently there has been renewed interest in automated method development in which the optimization software directly interfaces with the instrument in order to run or suggest new experiments based on the prior results that generated the initial resolution maps. In the late 1980s, a number of approaches to this problem were attempted, but none of these tools prevailed, due in part to the challenges of tracking peaks between experiments. 

All approaches to method optimization based on multiple experiments have the requirement that all components be detected and that they be tracked between runs. For complex samples, this is typically the most labor-intensive aspect of method development. For unattended method development, the instrument is required to monitor the change in retention of each component automatically. The historical limitations to this technology have been a key stumbling block in the widespread adoption of automated method development. 

Products/technologies The mixing routine of the FAMOS microsampling HPLC workstation enables automated method development for sample handling techniques of single beads to produce combinatorial libraries high-throughput is achieved by multiple analysis per vial. 

The method development process for on-line SPE is ideal for its ability to offer full automation. Method development involves the examination of several extraction variables with subsequent optimization. These parameters include the sorbent chemistry, the composition of the load, wash and elution solvents, sorbent particle size, solvent volumes, and flow rates. A general overview of the method development process for on-line SPE coupled to LC... 

The use of automation results in fast, easy, and reliable methods for SPE. There are a number of instruments available for totally automated SPE, as well as automated methods development of SPE, which span the spectrum in cost. In environmental applications, the choices of automation are limited, with only the Autotrace by Tekmar available for large-volume samples (1 L). In the area of on-line SPE-HPLC, nearly all of the workstations for SPE have the option for direct injection into the HPLC. For on-line SPE-GC/MS, there are several instruments and methods available (a modified PROSPEKT, Varian automated SPME, and the Hewlett-Packard solid-phase extraction workstation). For total automation including addition of internal standards, derivatiza-... 

Traditional, and perhaps, manual approaches for method development would be too time-consuming to perform within a drug discovery environment. As a result, automated method development routines, such as the procedure to generate optimized SRM tables for PK screening, are an essential requirement for drug discovery support [60],... 

ACD/Method Development Used as standalone version or together with Agilent or Hitachi HPLC automated method development systems. Able to import data from major chromatography data systems. Package of ACD/lab tools for data ... 

Objective functions are used primarily for computer ranking of separation quality in approaches for automated method development. For this purpose the separation quality throughout the chromatogram must be expressed by a single-valued and easily calculated mathematical function [202-209], This has proven to be a difficult problem and no universal solution has emerged. There is no straightforward manner to uniquely define the resolution of all peaks simultaneously by a single number. More likely, for... 

Advances in stationary phase technology have led to commercial availability of adsorbents such as high performance sihcas, aluminas, polyamides, celluloses and derivatised silicas [9,10], The development of automated method development (AMD) systems [127] now allow multi-step gradients of different elution strengths to be achieved in a relatively short time compared to earlier manual approaches. AMD systems are ideally suited for separation of complex mixtures with a wide range of polarities. Further improvements in sample resolution and reduced method development times in TLC include the use of two-dimensional development approaches [128] and forced-flow development by over-pressure liquid chromatography (OPLC) [129]. 

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