Bioanalysis Zone

Optimization of microflow LC–MS/MS and its utility in quantitative discovery bioanalysis

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Discovery bioanalysis is an integral part of drug discovery by providing analytical support for screening and characterization of adsorption, distribution, metabolism, excretion, pharmacokinetics (PK) and toxicokinetics of new chemical entities [1–3]. LC–MS/MS is the driving force in accomplishing a large amount of quantification work in discovery bioanalysis, owing to its unique capability of high-throughput, fast turnaround and high sensitivity [4–7]. To help achieve the goal of profiling and triaging for a large number of diverse compounds through various in vitro and in vivo screenings in drug discovery, the LC–MS/MS methods used in discovery bioanalysis are mainly ‘fit for purpose’, namely, to provide satisfactory data for the vast majority of compounds by utilizing a generic, ballistic gradient typically at a flow rate of 0.5–1.0 ml/min on columns with an inner diameter of 2.1–4.6 mm on conventional LC [8–10] in order to achieve a fast turnaround time of impactful data to guide further characterization of promising chemotypes. There are cases, however, where sensitivity requirements for the compounds are not met with these generic methods or workflow, examples of which include

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