Parallel LCMS

One of the most important recent innovations for discovery analytical support is parallel LC-MS with a multiplexed (MUX™) electrospray interface on an orthogonal time-of-flight (TOF) or a triple-quadrupole MS platform. The commercially available interface consists of four or eight multi-indexed rotating sprayers plus an extra fixed probe that is used to introduce an internal standard for exact mass measurement. Although the eluent from LC columns are simultaneously sprayed into the MS, the position of the sampling rotor allows the spray from only one probe to be admitted into the sampling cone [13]. An increasing number of applications have been reported due to its four-or eightfold increase of throughput for both qualitative and quantitative tasks, such as ADME analysis, structure characterization of proteins, peptides, and combinatorial libraries [14-17]. Recently, Eldridge et al. added eight evaporative light-scattering detectors (ELSD) onto this parallel LC-MS system for natural-product-libraries analysis to capture the structure information of those components that have no UV chromophores [18]. Two major concerns with this system are reduced sensitivity because of the limited cycle time per channel and the interchannel cross contamination. However, these concerns have been reported to be almost negligible for most applications [19,20].

A fully automated high throughput analysis platform that has been successfully established is shown in Figure 14.1. This platform is able to provide unattended, continuous operation, by control of the entire process (i.e., load plates, scan bar codes, sample injection, analysis, report generation, and data archival) with a single computer workstation [21]. The throughput is 1200 samples per day with acceptable chromatographic resolution. Moreover, when

FIGURE 14.1 Scheme of a fully automated high throughput analysis platform based on a MUX system.

combined with a sample pooling strategy, this system has also been used to determine lipophilicity (logP) [22] and protein-compound binding affinity [23]. Both systems have been validated for routine operation.

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