Parallel LC/MS analysis

Sage, A.B. Giles, K. High Throughput Parallel LC/MS Analysis of Multiple Liquid Streams. GIT Laboratory Journal 2000,4, 35-36. 

For a conventional single-channel LC/UV/MS system, a single unsatisfied well could be easily reanalyzed. In the eight parallel LC/UV/MS system, the rerun procedure was different from that of the single-spray system. If problems were found in a single channel, such as retention time shift or channel blockage, 12 wells in a row would fail and the whole plate had to be reanalyzed. We have developed a rerun protocol that made the parallel LC/MS analysis as efficient as the single-channel system. 

TABLE 6.6 Results of an n-in-one experiment of the parallel LC/MS analysis of 64 analytes from the same plasma sample ... 

The incorporation of four-column parallel F-HPLC coupled with a multichannel MS interface increased the speed both for sample analysis and sample demixing [56]. A 5 min analysis method for baseline separation of five components of M-79a-d was applied to four-channel parallel LC-MS analysis (see Scheme 13.18 and Figure 13.2). Four mixture samples containing a total of 20 compounds could be separated in 5 min, which dramatically improves the efficiency of FMS. 

Figure 4.16. (a) Pictures of an Eksigent Parallel LC system and (b) Waters 2488 eight-channel UV/Vis detector, (c) Schematic diagram of a multiplexed parallel LC/MS analysis. Diagrams courtesy of Eksigent and Waters Corporation. 

The issue is how LC/MS analysis—by nature a serial procedure—can meet the demands of parallelized sample generation and preparation. This can be achieved by speeding up the serial LC/MS, parallelizing parts of the analysis, or both. Several aspects of optimization should be considered ... 

The significant advantage of the parallel LC/MS system is its throughput. Because eight LC/UV/MS analyses can be conducted simultaneously, the total analysis time is decreased by a factor of eight. To analyze every compound in a library of 2500 compounds at 3.5 min cycle time requires 146 h using a single channel LC/UV/MS system. However, it requires only... 

Feng, B. McQueney, M. S. Mezzasalma, T. M. Slemmon, J. R. 2001. An integrated ten-pump, eight-channel parallel LC/MS system for automated high-throughput analysis of proteins. Anal. Chem, 73, 5691-5697. 

A schematic of a commercially available system that was conflgured in our laboratory for parallel analysis and purification is shown in Figure 11-9. This four-channel parallel LC/MS purification system consists of a binary HPLC system, an autosampler configured with four injection, a multichannel UV detector, a quadrupole mass spectrometer equipped with an MUX ion source which monitors four flow streams simultaneously, and four independently... 

LC/MS ANALYSIS OF HIGH-THROUGHPUT PARALLEL SYNTHESIS LIBRARIES... 

TOF and Q-TOF instraments are freqnently applied in metabolism studies. The identity of the epothilone B metabolites fonnd by precnrsor-ion analysis (Figure 10.5, Ch. 10.4.2) was confirmed using accnrate-mass determination on a LC-TOF-MS instmment [29]. Some other examples are the characterization of metabolites of moclobemide and remikiren [32], the identification of ketobemidone Phase-I and Phase-II metabolites [33], and the identification of in vitro metabolites of ethoxidine [34]. The nse of a five-channel multiplexed ESI interface (four chaimels for parallel LC-MS and one channel for lock-mass componnd infusion) on a Q-TOF instrument was recently described to speed np metabolite identification and to enhance the efficient nse of the costly instrument [35]. 

Cremin, P.A. Zeng, L. High-Throughput Analysis of Natural Product Compound Libraries by Parallel LC-MS Evaporative Light Scattering Detection, Anal. Chem. 74, 5492-5500 (2002). 

Organ, A. "MUX for Parallel LC/MS, Chemical and Pharmaceutical Structure Analysis (CPSA) symposium, Princeton, New Jersey, October 9-11,2001. 

The MS instrumentation is the most expensive part of the LC-MS system, hence efforts to improve the throughput of the LC-MS analysis often involve the use of parallel multiple columns that feed into a single mass spectrometer. Zeng and Kassel [99] developed an automated parallel analytical/preparative LC-MS workstation to increase the throughput for the characterization and purification of combinatorial libraries. The system incorporates two columns operated in parallel for both LC-MS analytical and preparative LC-MS purifications. A multiple-sprayer ESI interface was designed to support flows from multiple columns. The system is under complete software control and delivers the crude samples to the two HPLC columns from a single autosampler. The authors demonstrated characterization of more than 200 compounds per instrument per day, and purification of more than 200 compounds per instrument per night. De Biasi et al. [100] described a four-channel multiplexed... 

The prediction of the important structural features that affect intestinal permeability is useful information to obtain early in the drug discovery process. The two most common models used to obtain fast, high-throughput measurements are the parallel artificial membrane permeation assay (PAMPA) and the cell line assays that feature cultured human colon adenocarcinoma cells (Caco-2). Each method uses a surrogate model to mimic intestinal absorption followed by LC-MS analysis. 

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