On-site target library

During the set-up process of the GC/MS instrument that is shown in Picture 5, the negotiation module is used to install the on-site target library and to select the security level filter of AMDIS (this approach may be modified for the new GC/MS system). The security level filters of AMDIS progressively restrict the accessibility to and the content of the data that AMDIS provides after postprocessing of the spectral data. In order to protect... 

Figure 1 shows schematically the relationship between on-site target library, blinding, and AMDIS security level filter. 

No search of libraries other than on-site target library. 

AMDIS on-site version, mass spectral data analysis software, which is triggered at the end of each analysis run. This reduced on-site version of AMDIS only displays TICs and mass spectra of analytes that match a chemical in the on-site target library. 

The library search function is altered. AMDIS on-site version can only search in the on-site target library. 

The open version of AMDIS is only available when the instrument is operated in open mode. In addition to the functions of the on-site version of AMDIS as described above, the open version allows for displaying the entire chromatogram and the spectra of all peaks present in it. Chromatographic peaks and their spectra are shown independently from any match of the spectrum to the mass spectra present in the library used. The open version of AMDIS is not restricted to the use of the on-site target library onsite.msl but can utilize any other AMDIS library installed. 

If a system was returned from inspection, external exercise, or maintenance at the manufacturer, an additional test for cleanness (entrance control) is performed. Three different blank injections with solvent, BSTFA, and DMT are performed and evaluated using an on-site target library containing all MS spectra from the OCAD. Absence of any identification ensures that the system components are free from scheduled chemicals and their degradation products. The same blank injection tests are performed if a system in waiting status was used internally for injections other than check mixture. The on-site target library used in the test of cleanness is removed from the hard disk before issuing the system for a mission. 

As shown in Fig. 16.6, we planned to use a pre-registered combinatorial chemistry protocol (LJ0194) to synthesize the targeted library. PGVL Hub allowed us to easily search and load this pre-registered reaction scheme into a design session without the need to draw a reaction scheme required for product enumeration (see Fig. 16.7). Even for this simple reaction, a simple reaction scheme drawn by users may not be sufficient to ensure proper formation of product structures in the case where bonds associated with chiral centers are near the reactive sites on the reactants. 

The OPCW Laboratory performs functional tests on the authenticated, certified, and on-site analytical databases. These are tests that verify that the analytical database is functional. So far, this procedure is fully developed for the MS analytical databases. The electronic version of OCAD (which so far consists of MS analytical data only) is tested with the NIST MS Search/Analysis program. The on-site MS analytical databases are tested using AMDIS software. A NIST or AMDIS library is created and this becomes the target library for a library search. A search is performed on a newly measured MS spectrum (raw data files) containing a number of chemicals that are present in the target library. Identification of the targeted spectrum indicates that the created library is functional. 

A fragment has greater flexibility and better access to its receptor site on the target than do the more rigid and larger compounds of the natural and synthetic libraries. 

When information is available about the therapeutic target, either through known active compounds or when the 3D structure of the receptor site is known, then the emphasis is usually on focused or targeted libraries. For example, compounds can be selected on the basis of similarity to a known active or actives, on predicted activity according to a quantitative structure-activity relationship (QSAR), or on their predicted ability to be able to bind to a receptor. 

---