Bioanalysis high-throughput

Recent innovations in ionization techniques have allowed the development of ambient mass spectrometry. Mass spectra can be determined for samples in their native environment without sample preparation. Although the ambient mass spectrometry technique is still in its infancy, its potential for serving as a tool of choice for high-throughput bioanalysis is very encouraging. 

Another MS-based approach used in high-throughput bioanalysis utilizes a mass spectrometer equipped with several API spray probes. Each of the analytical columns in parallel is connected to a separate spray probe and each spray is sampled in rapid successions for data acquisition by the MS. A separate data hie for each spray is recorded. Several samples can be analyzed simultaneously on parallel columns5 6 in the course of a single chromatographic run. 

Another approach to increase HPLC speed is the use of higher temperatures. The viscosity of a typical mobile phase used in reversed-phase separation decreases as the column temperature is increased. This allows an HPLC system to operate at a higher flow rate without suffering too much from increased back pressure. Zirconia-based packing materials provide excellent physical and chemical stability. They have been used successfully for high-throughput bioanalysis at elevated temperatures.9... 

Automation using a robotic liquid handling system eliminated most of the tedious steps encountered with traditional manual extraction procedures. Automated 96-well SPE and LLE techniques using robotic liquid handlers have been successfully implemented to support high-throughput bioanalysis.5... 

Due to its simplicity and wide applicability, PPT is important for sample pretreatment in early drug discovery when generic extraction of mixtures of candidates is more important than sensitivity. As a generic technique, PPT is attractive for high-throughput bioanalysis because it offers fast sample preparation and easy automation and requires minimal manual labor. 

The recent need of new therapies, more selective, available to patients in a rapid manner has been the driving force of innovation in the area of high-throughput bioanalysis. 

With the advent of API sources, LC/MS/MS allows the facile development of quantitative methods that are sensitive, selective, robust, and amenable to the rapid analysis of a majority of small molecules. In order to achieve high-throughput bioanalysis in support of pharmacokinetic studies, many approaches have been reported utilizing automated sample preparation and reducing analysis time by pooling samples, parallel analysis, and fast chromatography. 25,26,152,153... 

O Connor, D., and Mortishire-Smith, R. (2006). High-throughput bioanalysis with simultaneous acquisition of metabolic route data using ultra performance liquid chromatography coupled with time-of-flight mass spectrometry. Anal. Bioanal. Chem. 385 114-121. 

High-throughput bioanalysis screening approaches involve the characterization of full-scan mass spectra and MS/MS properties to determine the predominant molecular and product ions, respectively. This information is useful for the selection of appropriate ions for selected reaction monitoring (SRM) experiments. Settings such as collision energies and collisionally induced dissociation (CID) pressure or gas thickness can be optimized as well. Typically, the most abundant product ion is selected for SRM. Various acquisition software programs are used to perform the experiment, display the results, and process the data in an automated fashion. 

Allanson, J. P. Biddlecombe, R. A. Jones, A. E. Pleasance, S. 1996. The use of automated solid phase extraction in the 96 well format for high throughput bioanalysis using liquid chromatography coupled to tandem mass spectrometry. Rapid Commun. Mass Spectrom., 10,811-816. 

Tan A, Hussain S, Vallee F (2009) Evaporation-free extraction and application in high-throughput bioanalysis by LC-MS/MS. LCGC North America 27 414 127... 

As presented in the two previous subsections, several viable options exist for high throughput bioanalysis. It is interesting to note that an issue seldom discussed is the relative cost of the reagents and supplies associated with the various methods. For example, the issue of high mobile-phase consumption/waste-stream production in TFC may be a concern. A similar situation occurs with... 

Biddlecombe, R.A. Benevides, C. Pleasance, S. A Clinical Trial on a Plate The Potential of 384-Well Format Solid Phase Extraction for High-Throughput Bioanalysis Using Liquid Chromatography/Tandem Mass Spectrometry, Rapid Commun. Mass Spectrom. 15, 33 0 (2001). 

DIRECT PLASMA AND HIGH-THROUGHPUT BIOANALYSIS OF DRUGS AND METABOLITES... 

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