Liquid chromatography parallel sample analysis

Korfmacher, W. A. Veals, J. Dunn-Meynell, K. Zhang, X. Tucker, G. et al. Demonstration of the capabilities of a parallel high performance liquid chromatography tandem mass spectrometry system for use in the analysis of drug discovery plasma samples. Rapid Commun Mass Spectrom 1999, 13, 1991-1998. 

A number of valuable methods of analysis are essentially batch processis themselves and cannot be operated on a continuous basis. Their use in an on line mode will then require frequent sampling and rapid presentation of the sample to the instrument followed by rapid analysis. It may be necessary to use a battery of analysers working in parallel to cope with the number of samples presented. A particularly important example of batch analysis is the use of gas-liquid chromatography. The power of this technique to provide rapid analysis of complex mixtures has led to its use for "monitoring many organic processes, and its integration into many chemical plants. 

K.A. Lin, C.C. Demonstration of the Capabilities of a Parallel High Performance Liquid Chromatography Tandem Mass Spectrometry System for Use in the Analysis of Drug Discovery Samples, Rapid Commun. Mass Spectrom. 13, 1991-1999 (1999). 

The first set of information generated from the ADME studies are the overall plasma profiles of total radioactivity (TRA) versus time which is compared to the plasma profile of parent versus time measured by a validated LC/MS/MS assay. For those drugs where the parent is the major component at all time points in plasma, the total radioactivity profile usually parallels the profile of the parent. Metabolie profiles of plasma samples generated at different time points by high-performance liquid chromatography (HPLC) analysis followed by radioactivity and mass spectrometric detection provide exposure-related information for parent and metabolites in humans and animal species. In addition, this profile provides information about metabolites that humans are exposed to and how this compares to exposures in animal species. 

Briefly, the workflow for these determinations is as follows preparation of a protein sample, parallel treatments of reduced and unreduced samples with iodoacetamide, digestion of proteins with trypsin, and analysis of peptides by Liquid Chromatography coupled with Mass Spectrometry (LC-MS). 

Both liquid and gas chromatographic techniques have been developed to improve this analysis. Suatoni and co-workers (78,79) have performed most of the work by utilizing liquid chromatography. Soulages and Brieva (80) developed a gas chromatographic analysis that relies on selective adsorption of components. The sample is split onto three parallel columns. The saturates content is determined from one column that has a mercuric perchlorate-perchloric acid absorber for oleflns and aromatics. The second column is merely a delayer for a portion of the total sample. The third column has a mercuric sulfate-sulfuric acid absorber to retain the oleflns. Figure 13.25 is a typical chromatogram from this system. 

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