Open-access systems

There are now numerous opportunities to purchase open-access systems and most companies offer a similar specification in available functions and sensitivity. For the purpose of describing a generic system here the Micromass/Waters version will be used as an example. 

In this example the open-access system was used to determine the success of the reactions and generate a purity profile before performing automated purification u.sing HPLC (Autoprep — see Chapter 8) on the now characterised crude samples. 

As FIA-MS and liquid chromatography mass spectrometry (LC-MS) become more pervasive in the analysis of compound libraries, open-access instrumentation is increasingly used in HTOS laboratories as well as in support of general medicinal chemistry. These open-access systems are most often used for reaction monitoring and optimization, and in some cases, for library quality control and synthesis product purification. 

Automated data processing, data reduction, spectral interpretation, and reporting are also integral parts of open-access sample analysis. Mallis et al. [33] described the use of an open-access system with e-mail capabilities to distribute processed data reports to the chemist. Several methods have been developed, including structure elucidation with in-source collision-induced dissociation (CID). 

MALDl instruments, particularly those with automated plate loading, can also be operated successfully as open-access systems. Recently, the MALDl-TOF system in the facility was replaced with a MALDl-TOF/TOF instrument so that interested researchers could undertake peptide sequencing (and other structural determinations) along with standard MALDl-TOF analyses. 

Entities involved in long-term contracts with electric utihties, such as fuel supphers and NUGs selling power to utihties, also have concerns that some utihties or industrial customers will not be able to honor their contracts under the new, more competitive system. Einahy, some utihties are concerned that they wih not be adequately reimbursed for opening up their transmission systems to competitors. The potential competitors in turn are concerned that utihties whl not provide unbiased access to their transmission systems if the utihties themselves are also in business of marketing power. There has also been some debate regarding which transmission facihties are eligible for open access. This is because some facihties are considered local distribution systems by utihties, which feel they should not be opened to competitors. 

The whole NMR imaging sensor system usually consists of a magnet, a shim system mounted inside the room-temperature bore of the magnet, a gradient system mounted inside the shim system and the rf coil mounted inside the gradient system. In the case of a saddle coil or a birdcage resonator, open access can be realized from the bottom to the top of the entire system with the coil diameter. 

Some LC/MS users adhere to isocratic separation because of the myths around gradient elution (it is complex to develop and transfer between instruments and laboratories, it is inherently slower than isocratic methods because of re-equilibration, and other reasons summarized by Carr and Schelling6). A researcher may have a very good reason to use an isocratic method, for example, for a well defined mixture containing only a few compounds. The isocratic method would certainly not be useful in an open access LC/MS system processing varying samples from injection to injection. 

Gardner E. System opens access to physicians, restricts it to others, sidebar. Mod Healthcare 38, Nov. 3, 1989. 

Also, there is serious question as to whether such a system would be capable of obtaining a RCRA Part B Permit to operate without formal air emission control systems. These open tank systems are designed to be crude but effective. When one begins to collect flammable and toxic gases over such open tanks and to allow access of fork lift trucks to deliver and retrieve hoppers of slag, the logic of the system falls apart very quickly and one returns to the reactor concept or other options. 

Structure Confirmation In the open-access LC/MS procedure described by Pullen and co-workers, the samples are directly introduced from solution for ease of automation and sample preparation. Chemists prepare samples in solvent to a suggested concentration range, then log the samples into the system. The sample log-in is done at any time during the continuous automated queue. Autosampler vials are used to hold the samples, and autosamplers are used to... 

The LC/MS analyses were performed with either thermospray ionization (TSI) or particle beam (PB) interfaces. These systems successfully analyzed the labile, polar, or higher mass compounds, whereas a complementary gas chromatography (GC)/MS system was used for volatile compounds. The LC/MS system proved to be widely applicable to a range of chemically diverse compounds. The TSI and PB systems were both successful for 80-90% of the compounds analyzed. Automated, open-access LC/MS analyses performed well because sample throughput was expected to reach 250,000 in 1995. This throughput corresponds to approximately 1000 samples per day. 

Development of the method involved the installation of a system in an existing mass spectrometry laboratory and working with chemists for 3 months to determine specific needs and to develop a consistent, reliable procedure. The instrument was moved to an open-access laboratory and chemists were trained in its use. A key to making this approach a success is the fact that instrument downtime was kept to a minimum. Understandably, maintenance is done at off-peak times, and support mechanisms are put in place so problems are immediately addressed. Training and education was highlighted as a key factor for the successful implementation of this LC/MS system to optimize performance and to reduce the possibility of instrument contamination. 

In 1995, Taylor and co-workers also described the use of an open-access LC/MS system for routine structure confirmation, featuring atmospheric pressure chemical ionization (APCI). This system featured dual personal computers (PCs) for automated instrument control and sample log-in. A system-PC is responsible for running the Windows NT for Workgroups operating system and interfaces with the network for instrument control. A separate log-in PC, isolated from the LC/MS system, is used by the synthetic chemist to enter details about the samples. The analyst prepares the sample in an autosampler vial in one of several solvent options. The system specifies where to place the sample vial in the autosampler, and following analysis with a standard method, spectra are automatically processed and printed without any chemist intervention. 

Taylor and co-workers further demonstrated the value of open-access LC/MS systems for generating a widened scope of pharmaceutical analysis applications, including (1) characterization of synthetic intermediates and target compounds (2) reaction monitoring (3) reaction optimization (4) analysis of preparative HPLC fractions and (5) analysis of thin layer chromatography (TLC) plate spots. The availability of these methods led to the increased use of LC/MS for structural analysis. The short analysis time and reliable structure confirmation resulted in the use of LC/MS as a first choice for structure characterization for synthetic chemistry applications, as well as an expanded, and perhaps, integrated role of sample generator and analyst. 

Figure 6.16 Software packages for data manipulation and processing, using standalone computers and servers that are networked with open-access mass spectrometer data systems. (Reprinted with permission from Tong et al., 1998. Copyright 1998 Elsevier.)...

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