Drug discovery bioanalytical assays

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. 

Korfmacher, W. Bioanalytical assays in a drug discovery environment, in Using Mass Spectrometry for Drug Metabolism Studies, CRC Press, Boca Raton, 2005, pp 1-34. 

TABLE 2.1. Recommendations to Engineer Quality into Fit-for-Purpose Bioanalytical Assay Characterization in Drug Discovery... 

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). 

Strategies and Techniques for Bioanalytical Assays as Part of New Drug Discovery... 

FIGURE 1.14 Discovery PK analysis flowchart showing the multiple steps that are involved from the animal dosing to the HPLC-MS/MS assay followed by the report preparation and the electronic delivery of the report to the discovery team. (Reprinted from Korfmacher, W., Bioanalytical assays in a drug discovery environment, in Using Mass Spectrometry for Drug Metabolism Studies, Korfmacher, W. (ed.), CRC Press, Boca Raton, FL, 2005, p. 1. With permission.)... 

Wang, L. et al., LC-electrolyte effects improve the bioanalytical performance of liquid chromatography/tandem mass spectrometric assays in supporting pharmacokinetic study for drug discovery, Rapid Commun. Mass Spectrom., 21(16), 2573, 2007. 

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. 

MS/MS) is the standard detector for bioanalytical assays and drug discovery screening, its use for routine assays of drug substances and products is still limited due to its high cost and lower precision. Nevertheless, LC/MS/MS methods are increasingly used for ultra trace analysis or screening of complex samples. Other detection options include conductivity detection for ionic species and electrochemical detection for neuroactive species in biochemical research. 

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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