Bioanalytical applications drug discovery

Mei H, Hseih Y, Nardo C, Xu X, Wang S, et al. 2003. Investigation of matrix effects in bioanalytical high performance liquid chromatography/tandem, mass spectrometrometic assay application to drug discovery. Rapid Commun Mass Spectrom 17 97-103. 

Figure 2.7. Studies requiring bioanalytical quantitation during drug discovery and development. (GLP, Good laboratory practices IND, Investigational new drug application.)...

H. Mei, Y. Hsieh, C. Nardo, X. Xu, S. Wang, K. Ng, and W. A. Korfmacher, Investigation of matrix effects in bioanalytical high-performance liqnid chromatogra-phy/tandem mass spectrometric assays Application to drug discovery. Rapid Commun. Mass Spectrom. 17 (2003), 97-103. 

Mei, H. Hsieh, Y Nardo, C. Xu, X. Wang, S. Ng, K. Korfmacher, W.A. Investigation of Matrix Effects in Bioanalytical High-Performance Liquid Chromatography/Tandem Mass Spectrometric Assays Application to Drug Discovery, Rapid Commun. Mass Spectrom. 17, 97-103 (2003). 

The distinctions within the drug-discovery environment previously noted naturally favor the use of simpler and faster sample-preparation techniques. However, most all sample-preparation methods are potentially viable choices, as recent applications have demonstrated method-development techniques that are both rapid and selective. Also, there is value for the quick development of a bioanalytical method with selectivity for a series of similarly related structures, as that one method can often meet the needs for PK and toxicokinetic (TK) studies well into the discovery process, rather than just for one initial study. The variety of sample-preparation methodologies for bioanalysis are now detailed. 

Xu et al. [43] published a report on a process for rapid HPLC-MS/MS method development in a drug discovery setting. In this report, the authors provided a three-step process for rapid bioanalytical method development for HPLC-MS/MS methods suitable for drug discovery PK applications. Figure 1.10 shows the flowchart... 

This chapter reviews the use of HPLC in pharmaceutical analysis from drug discovery to quality control. The focus is on HPLC analysis of drug substances (DS) and products (DP) such as assay for potency, purity evaluation, and dissolution testing. A case study of the various HPLC methods used during early clinical development illustrates the versatility of this technique. Detailed descriptions of HPLC applications in pharmaceutical development and LC/MS analysis in drug discovery and bioanalytical studies can be found elsewhere.1-6 The regulatory aspects in pharmaceutical testing are covered in Chapter 9. 

Yu, R.Z., Geary, R.S., and Levin, A.A. (2004) Application of novel quantitative bioanalytical methods for pharmacokinetic and pharmacokinetic/pharmacodynamic assessments of antisense oligonucleotides. Current Opinion in Drug Discovery and Development, 7, 195 203. 

Given the foregoing discussion of some of the unique characteristics of macromolecules that lead to clear differences in their pharmacokinetics compared to those typical of small-molecule drugs, there is a subset of the entire group of bioanalytical assay validation parameters that are of key importance in support of pharmacokinetics of candidate macromolecular therapeutics. Assuming demonstration of accuracy and precision of sufficient quality for the intended application of the assay (e.g., non-GLP discovery support or GLP toxicokinetic support, as discussed above), the most important characteristics of a given assay in support of pharmacokinetic studies are likely to be selectivity, specificity, and reproducibility for analysis of incurred samples. These are all related to the ability of the LBA to detect and quantitate solely, or as closely as possible to solely, the analyte of interest. 

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