Drugs bioanalytical analysis

Korfmacher, W.A., Bioanalytical analysis in a drug discovery environment. In W.A. Korfmacher (Ed.), Using Mass Spectrometry for Drug Metabolism Studies, Boca Raton, FL CRC Press, pp. 1-34, 2005. 

Internal standardization methods are common for bioanalytical analysis of drugs in physiological fluids or complex samples requiring extensive sample work-up to compensate for loss occurring in preparation. The internal standard should have similar structures to the analytes and is added before sample work-up. For UV detection, the internal standard must be resolved from any potential sample components. In most bioanalytical LC/MS assays, isotopically labeled analytes (e.g., deuterated analytes) are commonly used. 

Moreover, MEEKC has been shown to be a highly apphcable system for the analysis of complex mixtures such as mirlticomponent formirlations, related substances of active principles and excipients in birlk drugs, chiral analysis, natural products, and bioanalytical separations. 

The features described above, when elegantly combined with column switching, become a powerful tool for direct analysis of biofluids in a fully automated, multidimensional way. This selective stationary phase has found application in a number of areas, such as bioanalytical quantification of drugs [11], analysis of endogenous peptides [29], and immunoassay techniques [29, 30]. 

There will be a continued need for enantiospecific methods of preparation and analysis, not only to ensure the quality of the final drug substance and reference materials, but also to control starting materials used for their manufacture, and key intermediates during synthesis. Likewise, specific and sensitive bioanalytical methods will be required to follow the fate of individual enantiomers after their administration. 

Typically, a PK study is composed of three phases, namely the in-life phase, bioanalysis, and data analysis. The in-life phase includes administering the compound to animals or humans and collecting samples from an appropriate matrix of interest such as blood or urine at predetermined time intervals for bioanalysis. The bioanalytical phase involves analysis of a drug and/or its metabohte(s) concentration in blood, plasma, serum, or urine. This analysis typically involves sample extraction and detection of analytes via LC-MS/MS. The third phase is data analysis using noncompartmental or compartmental PK computational methods. 

As of this writing, it remains to be seen whether the great speed potential of MALDI and DIOS for the quantitative analysis of drug molecules will be realized in practice. There are hurdles typical of any emerging application that need to be addressed. The need for providing rapid quantitative analysis of drugs is only becoming more acute, and as such, it is likely that DI techniques will become more prevalent in the area of small molecule bioanalytical MS. 

Bioanalytical Methods for Macromolecule Drug Analysis Common Considerations... 

Hou W, Watters JW, McLeod HL (2004) Simple and rapid docetaxel assay in human plasma by protein precipitation and high-performance liquid chromatography-tandem mass spectrometry. Journal of Chromatography B 804 263-267 Schuhmacher J, Zimmer D, Tesche F, Pickard V (2003) Matrix effects during analysis of plasma samples by electrospray and atmospheric pressure chemical ionization mass spectrometry practical approaches to their elimination. Rapid Communications in Mass Spectrometry 17 1950-1957 Shah PW (2001) Guidance for Industry Bioanalytical Method Validation U.S. Department of Health and Human Services, Food and Drug Administration... 

Applications of HPLC Of the bioanalytical separation technologies described in this book, arguably HPLC has the widest range of applications, being adopted for the purpose of clinical, environmental, forensic, industrial, pharmaceutical and research analyses. While there are literally thousands of different applications, a few indicators of how HPLC has been used are as follows (i) Clinical quantification of drugs in body fluids (ii) Environmental identification of chemicals in drinking water (iii) Forensic analysis of textile dyes (iv) Industrial stability of compounds in food products (v) Pharmaceutical quality control and shelf-life of a synthetic drug product (vi) Research separation and isolation of components from natural samples from animals and plants. 

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