Sample preparation for bioanalysis

Deng, Y. et al. 2002. High-speed gradient parallel liquid chromatography/tandem mass spectrometry with fully automated sample preparation for bioanalysis 30 seconds per sample from plasma. Rapid Commun. Mass Spectrom. 16 1116. 

Deng, Y Wu, J.-T, Lloyd, T.L. Chi, C.L. Olah, TV. Unger, S.E. Highspeed Gradient Parallel Liquid Chromatography/Tandem Mass Spectrometry with Fully Automated Sample Preparation for Bioanalysis 30 Seconds per Sample from Plasma, Rapid Commun. Mass Spectrom. 16, 1116-1123 (2002). 

High-speed gradient parallel HPLC-MS/MS has been successfully used with fully automated sample preparation for bioanalysis. These techniques typically use a MUX interface and can provide analysis times as low as 30 s per sample. This technique suffers from instrument complexity that have dramatic consequences is system ruggedness [53],... 

New developments in integrated sample preparation for bioanalysis. In Wilson ID (ed) Bioanalytical separations. Elsevier, Amsterdam... 

Chang, M. S., Ji, Q., Zhang, J., and El-Shourbagy, T. A. (2007a). Historical review of sample preparation for chromatographic bioanalysis Pros and cons. Drug Dev. Res. 68 107-133. 

Wells, D.A., Sample preparation for drug discovery bioanalysis, in Integrated Strategies for Drug Discovery Using Mass Spectrometry, Lee, M.S., Ed., John Wiley Sons, Inc. New York, 2005, p.477. 

Jemal M (2000) High-throughput quantitative bioanalysis by LC/MS/MS. Biomedical Chromatography 14 422-429. Kataoka H (2003) New trends in sample preparation for clinical and pharmaceutical analysis. Trends in Analytical Chemistry 22 232-244. 

This chapter will review recent advances in mass spectrometry, liquid chromatography, and sample preparation techniques that aim at achieving high throughput. In particular, online solid phase extraction and multiplexed HPLC front ends for quantitative bioanalysis will be discussed in detail. 

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. 

Because the instability of the N-oxide metabolite, which was subjected to decomposition during sample preparation (solvent evaporation during offline SPE), online SPE LC/MS became the method of choice for the application. Hsieh et al. (2004) built a system with two TFC cartridges and one analytical column, and another system with two TFC cartridges and two analytical columns for GLP quantitative bioanalysis of drug candidates. A Turbo C18 (50 x 1.0 mm, 5 /.mi, Cohesive Technologies), an Xterra MS C18 (30 x 2.0 mm, 2.5 /mi), and a guard column were used. Protein precipitation preceded injection. The cycle times for the two systems were 0.8 and 0.4 min. 

The high-throughput concept for quantitative bioanalysis applies to steps such as assay development, sample collection and sorting, sample preparation, sample analysis, and data processing and reporting. Those processes are closely interlinked and improvement of process throughput is equally important. 

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 applicability of cinchonan carbamate CSPs for bioanalytical investigations using HPLC-ESI-MS/MS has been demonstrated by Fakt et al. [120]. The goal was the stereoselective bioanalysis of (R)-3-amino-2-fluoropropylphosphinic acid, a y-aminobutyric acid (GABA) receptor agonist, in blood plasma in order to determine whether this active enantiomer is in vivo converted to the 5-enantiomer. In this enantioselective HPLC-MS/MS bioassay, sample preparation consisted of... 

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