Drug bioanalysis structures

Figure 3. Typical rcvcrsc-phasc-type chromatogram of a diastereomer separation of an aminoelhanol, in this case (ft.S)-propranolol, using an (ft.Si-structure homolog as the internal standard and derivatized with (ft.ft)-DATAAN (Table , Entry 25). This example represents an application for the bioanalysis of a betablocking drug (propranolol), but it can also be used for bulk compound analysis for optical purity determinations.

Because of the widespread use of LC/MS/MS for drug discovery bioanalysis, there is currently less of a necessity for finely tuned solid-phase extractions than there once was in this area. Instead, generic solid-phase extraction conditions that can accommodate many different analyte structures using the same extraction conditions have become more interesting. To make a solid-phase sample preparation useful for LC/MS/MS it must remove as much of the sample salts as possible in order to reduce the effects of ion suppression [47,51—52] and it must remove as many nonvolatile matrix components as possible so that the instrument ion source is not quickly fouled. Because the LC/MS/MS instrument is inherently so selective, added assay selectivity, per se, is no longer an objective of solid-phase extraction. 

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. 

MS-MS is currently very widely used in combination with chromatographic separation methods, especially LC. The obvious reason for this is the frequent use of soft ionization techniques in LC-MS interfacing, i.e. electrospray and atmospheric-pressure chemical ionization. MS-MS allows additional structural information as well as the molecular mass information to be obtained. On-line LC-MS-MS is currently the method-of-choice in quantitative bioanalysis in (pre-) clinical pharmacological studies during drug development in pharmaceutical industries. In these studies, the instrument is operated in... 

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