Pharmacokinetic proteomics

Pharmacokinetic proteomics (ADME analysis, formulation, stability studies, and pharmacokinetics). 

Mass spectrometry (MS) is playing an increasingly visible role in the molecular characterization of combinatorial libraries, natural products, drug metabolism and pharmacokinetics, toxicology and forensic investigations, and proteomics. Toward this end, electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric pressure photo-ionization (APPI) have proven valuable for both qualitative and quantitative screening of small molecules (e.g., pharmaceutical products) [9-14]. 

There are two main reasons for entering the realm of micro- and nano-LC to obtain necessary sensitivity or if only the smallest quantities of samples are available. The main fields of application are currently proteomics, pharmacokinetics, metabolism studies, microdialysis, and, increasingly, environmental analysis. Flow rates in micro- (2-50 pL min ) and nano-LC (200-2000 nL min ) place high demands on the HPLC system and the user. Continuous optimization with regard to robustness, sensitivity, detection limit, and resolution tends to be a feature of any application. 

Storage allows more ions to be trapped than in a conventional 3D-IT instrument (see the following text). This, together with the axial ion detection, significantly increases the sensitivity of ion detection. Therefore, LTQ mass analyzers are more and more often used in areas where sensitivity is a crucial issue, such as pharmacokinetics and proteomics (including, e.g., posttranslational modification studies). 

Part V targets applications that are organized according to specific compound classes of analytes. The role of mass spectrometry in peptide and protein characterization and in proteomics is the subject of Chapter 18. Next, the topic of carbohydrate analysis by ESI and MALDI is tackled in Chapter 19. This is followed by an examination of ESI and MALDI applications to lipid analysis (Chapter 20). Finally, the important subject of drug discovery is addressed in Chapter 21, including in vitro ADME (absorption, distribution, metabolism and excretion) profiling and pharmacokinetic screening. 

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