Quantitative bioanalysis: an integrated approach for drug discovery and development

Ong, Voon; Cook, Kevin L.; Kosara, Christine M.; Brubaker, William F.

doi:10.1016/j.ijms.2004.01.021

Cited by 19 publications

(8 citation statements)

References 31 publications

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“…However, a variety of high quality analytical columns are now available on the market, stable up to pH 10-11 suitable for -TFC methods. This includes both spherical particle silica based columns [3] and monolithic columns [11,13].…”

Section: Applicability As a Routine Methodsmentioning

confidence: 99%

“…Turbulent flow chromatography (TFC) is an online application that enables quantitative determination without prior sample cleanup and the technology is well described within the literature using a variety of biofluids [1][2][3][4][5][6][7], predominantly coupled to a tandem mass spectrometric endpoint (TFC-MS/MS). The ability to dilute and inject samples online with minimal intervention reduces the preparation time necessary and consequently offers * Corresponding author.…”

Section: Introductionmentioning

confidence: 99%

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Development of a μ-turbulent flow chromatography focus mode method for drug quantitation in discovery bioanalysis

Turnpenny

Fraier

Chassaing

et al. 2007

Journal of Chromatography B

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Section: Applicability As a Routine Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of a μ-turbulent flow chromatography focus mode method for drug quantitation in discovery bioanalysis

Turnpenny

Fraier

Chassaing

et al. 2007

Journal of Chromatography B

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“…Hence, it warrants the screening of selected lead compounds in preclinical species such as rats, mice, dog, pig and monkey, before progressing to clinic [83,84]. Role of LC-MS/MS in performing bioanalysis of pharmacokinetic samples was well reported in the literature [85][86][87][88].…”

Section: Pharmacokinetic Analysismentioning

confidence: 99%

Mass Spectrometry as a Workhorse for Preclinical Drug Discovery: Special Emphasis on Drug Metabolism and Pharmacokinetics

Veeravalli¹,

Madgula²,

Srivastava³

2019

Mass Spectrometry - Future Perceptions and Applications

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Mass spectrometry as an instrument is popular, given its sensitivity, selectivity, speed and robustness. In this chapter, we have briefly deliberated on various mass spec platforms, their hardware components and specific applications in preclinical drug discovery with a special emphasis on drug metabolism and pharmacokinetic assays. Basic principle of operation of mass spectrometer and various ionization techniques/mass analyzers was explicitly discussed. Compatibility of mass spectrometers with ultrafast LC and various throughput techniques, enabled evaluation of thousands of compounds with quick turnaround times. Faster generation of results corresponding to in vitro ADME and in vivo pharmacokinetic assays, aid medicinal chemists to refine their combinatorial synthetic chemistry efforts and expedite the lead optimization and identification phases of drug discovery. Mass spectrometer is a powerful tool for both qualitative and quantitative applications. While quantitative applications include measurement of absolute/relative concentrations, qualitative features assist in identification of molecular structures of metabolites and putative biotransformation pathways. Qualitative inputs are more precise and accurate, with the advent of high-resolution mass spectrometry technology. Although, mass spectrometry has many built-in advantages, it also suffers from matrix effects, as the samples analyzed are mostly of biological origin and are complex in nature. In this chapter, we have defined the nature of matrix effects and various approaches by which these matrix effects can be mitigated.

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“…We have also recently used Turbo-Flow to confirm the presence of a drug in a series of post-mortem specimens (whole blood, vitreous humour and stomach contents) following simple PPT and dilution with aqueous buffer (Fisher et al, 2012). TurboFlow sample preparation has further been used for a number of in vitro studies during drug discovery and development (Ong et al, 2004;Smalley et al, 2007;Schebb et al, 2011a).…”

Section: Alternative Matricesmentioning

confidence: 99%

Turbulent flow chromatography in bioanalysis: a review

Couchman¹

2012

Biomedical Chromatography

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With advances in fast chromatography techniques, and highly sensitive and selective detection methods such as tandem mass spectrometry, very high-throughput bioanalytical methods can now be easily developed. The bottleneck of the analytical process then becomes the sample preparation, which it is now realized is crucial to the robust operation of the analytical system, especially for quantitative assays. Turbulent flow liquid chromatography was developed in the late 1990s, and combines 'size exclusion' and traditional stationary phase column chemistry to separate macromolecules, such as proteins, from smaller molecules and analytes of interest in biological fluids. By definition, the process is very rapid, and the instrumentation and software have been developed for fully automated, on-line extraction of neat biological fluids. This work aims to review the chromatographic theory of turbulent flow chromatography and illustrate, using examples from recent literature, the application of this technique to a range of analytes from a number of different biological matrices.

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Quantitative bioanalysis: an integrated approach for drug discovery and development

Cited by 19 publications

References 31 publications

Development of a μ-turbulent flow chromatography focus mode method for drug quantitation in discovery bioanalysis

Development of a μ-turbulent flow chromatography focus mode method for drug quantitation in discovery bioanalysis

Mass Spectrometry as a Workhorse for Preclinical Drug Discovery: Special Emphasis on Drug Metabolism and Pharmacokinetics

Turbulent flow chromatography in bioanalysis: a review

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