Profile groups

Quite often the profiling group initiates the activities of compound management and coordinate the preparation of biological material from cell biology. This may require one to three... 

To assist with the MS/MS structure identification, the gross substructure of buspirone is categorized into profile groups (Kerns et al., 1995). Profile groups directly correlate specific product ions and neutral losses with the presence, absence, substitution, and molecular connectivity (Lee et al., 1996) of specific buspirone substructures and their modifications. The profile groups of buspirone are identified with abbreviations that correspond to the three specific substructures azaspirone decane dione (A), butyl piperazine (B), and pyrimidine (P). Substituted substructures are designated with a subscript ( ), and a dash (-) denotes substructure connectivity. Thus, the buspirone molecule is represented by A-B-P. The As-B-P designation... 

Table 6.11 illustrates a representative buspirone metabolite structure database. Information on the structure, molecular weight, UV characteristics, RRT, and product ions of metabolites obtained from rat bile, urine, and liver S9 samples are compiled. Using this format, the predominant buspirone metabolite profile groups, As-B-P, A-B-Ps, and As-B-Ps are easily recognized. These profile groups indicate azaspirone decane dione and pyrimidine as metabolically active sites of attack and the presence of multiple substitution sites on each of these substructures. In many cases, the profile groups indicate the occurrence of metabolic reactions on more than one substructure. 

Table 6.13 summarizes the novel taxane structures identified with LC/MS. These impurities incorporate several consistent structural variations from the five profile groups of paclitaxel (Figure 6.29). Nearly all of the compounds contain the characteristic paclitaxel... 

Figure 6.29 General structures of the five profile groups observed using LC/MS, based on the paclitaxel template. (Reprinted with permission from Kerns et al., 1995. Copyright 1995 John Wiley Sons.)...

During the development of TAXOL , 90 taxane impurities were rapidly identified and added to the structure database. This MS/MS information is routinely obtained for impurities down to the 100 ng level (injected), and requires approximately 2-3 h for the analysis of each sample. The compounds are structurally categorized with profile group terminology. The LC/MS-based methods are significantly faster than previous methods based on scale-up, isolation, fractionation, and individual structural analysis. 

Species DNA base composition Multivariate analysis group No. FAME profile group No. ... 

Of the 293 patients in the control group 33 (11.3%) had blood taken for biochemical or hematological tests within the profile group these tests requested would represent 1.2% of the total tests if all the control group had full profiles performed. In the patients profiled the practitioners had... 

Unsuspected biochemical abnormalities such as hypercholesterolemia in 17 patients and hyperuricacidemia in four patients were recorded as unexplained abnormal results, not as diagnostic results, since treatment was not considered necessary for such patients. In 57 (19.3%) of the patients in the profile group the serum potassium levels were over 5 mEq/1 most of these were thought to result from hemolysis and were therefore marked as expected abnormalities. 

MoA into one of the known MoAs of the GEP Compendium with a single experiment. Arahidopsis plants are sprayed with the respective compound and the isolated and labeled RNA is analyzed on the Arahidopsis chip. Subsequently, the resulting expression profile is compared with those in the compendium. This comparison is done by supervised learning algorithms like Support Vector Machine (SVM) [15] or Analysis of Variance (ANOVA) [16]. When the new expression profile groups together with profiles of a specific MoA in the compendium there is an utmost probability that the corresponding compound has the same MoA (Fig. 33.4). If necessary, the MoA can be verified by classical methods such as enzyme assays or supplementation tests, if available. 

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