HPLC systems parallel

We developed a staggered parallel HPLC system with a CTC HTS PAL autosampler equipped with trio valves. The system consists of four (six if gradient is needed) independent HPLC pumps. Parallel analysis is achieved by an offset dual-stream system with a time delay that allows efficient staggering of MS acquisition times. 

Staggered parallel chromatography is an efficient and capable tool for linking multiple HPLC systems to a serial detection device, the mass spectrometer. The LC2MS version of the LCnMS approach has been in continuous use since 1998 in our laboratory and has supported hundreds of studies. The LCnMS scheme is now available from many commercial venders. However, for users who want to utilize existing equipment and not purchase additional equipment, it is beneficial to configure an ad hoc system from standard HPLC equipment as presented in this chapter. 

One drawback of this approach is the relatively low sample throughput of traditional HPLC systems. The primary reason for this low throughput is that each standard and sample must be assayed under a minimum of three different isocratic conditions. Assuming a run time (injection to injection) of 10 min, it would take 50 hr to analyze 4 standards and 96 unknowns. /./PLC is ideally suited for determination of log P since it facilitates parallel analysis of a large number of compounds under identical chromatographic conditions (Table 6.4). 

The focus of this chapter has been on the synthesis of new catalysts by parallel and combinatorial methods. Another aspect important to the development of new catalysts by these methods is the screening of these large libraries. We will not attempt to cover this topic comprehensively but do feel it is necessary to summarize some of the approaches that have been taken. Methods for screening libraries can be divided into both serial and parallel methods. Generally, the serial methods are adaptations of standard methods that allow for rapid individual analysis of each member of a library. Serial approaches for the analysis of libraries can be as simple as use of an auto sampler on a GC or HPLC system or as advanced as laser-induced resonance-enhanced multiphoton ionization of reaction products above the head-space of a catalyst (16) or microprobe sampling MS (63). The determination of en-antioselectivity in catalysis is a particular problem. Reetz et al. (64) reported the use of pseudoenantiomers and MS in the screening of enantioselective catalysis while Finn and co-workers (65) used diastereoselective derivatization followed by MS to measure ee. 

Multichannel HPLC—HPLC system designed to run parallel HPLC columns into a multi-flow cell UV or fluorescent detector. Designed for production laboratories to speed QA/QC monitoring (see Chapter 16). 

Performing parallel analysis of compound libraries offers many potential advantages over serial-based LC/MS analytical methods, the most obvious of which is dramatically increased compound analysis throughput. Using singlechannel HPLC-based purification systems, routine sample throughput of up to 192 reaction mixtures per 24-hour day was reported [64]. With parallel HPLC systems, it has been reported that the theoretical throughput increases to 384 samples per day for a two-channel system and to 768 samples per day for a four-channel system. 

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... 

The development of the first HPLC system with MW-triggered fraction collection was described by Zeng et al. [50] at CombiChem. This system was a dual analytical-preparative instrument with parallel-column format, termed parallel Analyl/PrepLCMS." developed by the modification of commercially available instrumentation. This system had software-controlled valves that applied sample to each path from a single autosampler and had the capacity to purify and analyze more than 100 samples per day. Initial analytical LC-MS data acquired by the system allowed the identification of samples that require... 

Parallel analysis is one of the most effective ways to enhance laboratory productivity. A typical parallel analysis HPLC system consists of multiple pumps or a multi-channel pumping system, a multi-probe autosampler capable of four or eight simultaneous parallel injections from 96-well microplates, and a multiplexed UV detector and/or MS. This generic approach allows a 4 to 8 fold increase of sample throughput while maintaining the traditional performance and convenience of HPLC. This technology can potentially be extended to a 96-channel analysis system. 

Low dispersion, ultra-high-pressure HPLC systems, multidimensional LC and parallel analysis... 

If HPLC purification is necessary, a one-column system can purify about 100 samples in milligram scale in one day. In this case, it is advantageous to use a LC-MS system where the fraction collector is driven by the mass spectroscopic information, because all fractions are already analyzed, and ideally a reformatting step in the 96-well format is not required. Commercially available HPLC-systems using more than one column in parallel are few in number. One system from Biotage consists of four columns driven by one pump and an individual fraction collector for each column. However, the system is not connected online to a mass spectrometer, and all fractions have to be analyzed offline by mass spectrometry. This may cause difficulties in sample-tracking and reformating into the 96-well format, which should be controlled by appropriate software. 

---