Data-dependent accurate

After all four positive scans are completed (typically within 3 s), the polarity is switched and the fifth scan event records a negative-ion full-scan MS. If the expected protonated molecule is not detected in the positive mode, the second, third and fourth scan events are skipped and the fifth (negative-ion-mode) scan event is triggered. Similar to the positive-ion mode, if the expected [M-H]- ion is detected in the full-scan MS, IT data-dependent MS/MS (sixth), FT accurate MS (seventh), and FT MS/MS (eighth) scan events are acquired. Clearly demonstrated here is the ability of the LTQ-FT to handle multiple experiments on a chromatographic time scale. One might question the need for such an elaborate data-dependent scheme when apparently all that is needed is an accurate mass determination followed by a data-dependent accurate mass MS/MS spectmm. Apart from the fact that using the... 

Figure 5.9. LC-MS (TIC) and UV (220 nm) chromatograms for microsomal incubation of verapamil containing parent molecule and detected metabolites. Data-dependent accurate mass measurements for verapamil, metabolite parents and fragment ions are shown in the inset.

Lim, H. K., Chen, J., Sensenhauser, C., Cook, K., and Subrahmanyam, V. (2007). Metabolite identification by data-dependent accurate mass spectrometric analysis at resolving power of 60,000 in external calibration mode using an LTQ/Orbitrap. Rapid Commun. Mass Spectrom. 21 1821-1832. 

Peterman, S. M., Duczak, N., Jr., Kalgutkar, A. S., Lame, M. E., and Soglia, J. R. (2006). Application of a linear ion trap/orbitrap mass spectrometer in metabohte characterization studies Examination of the human liver microsomal metabolism of the non-tricyclic antidepressant nefazodone using data-dependent accurate mass measurements. J. Am. Soc. Mass Spectrom. 17 363-375. 

Either the information obtained during the data-dependent acquisition is sufficient or a fraction of interest can be re-analyzed by chip-based infusion at a flow rate ca. 200 nl min. Due to the miniaturization sample consumption is very low (typically 1-3 pi) and acquisition time is no longer critical. Therefore various MS experiments can be performed on various instruments, including MS and accurate mass measurements. An additional advantage is that the eluent can be removed and the infusion solvent can be optimized for positive or negative ion detection or for deuterium exchange measurements. 

A similar approach using accurate mass measurements and predictive fragmentation sofiware was also applied for the examination of the human microsomal metabolism of nefazodone using a linear ion trap-orbitrap hybrid mass spectrometer. Based on a single LC-MS run, using data-dependant acquisition, 15 metabolites of nefazodone could be identified in MS and MS/MS with a mass accuracy better than 3 ppm. 

An essential step forward was also the development of kinetic models for electron tunneling reactions in solids [20-25]. Kinetic equations corresponding to these models were found to describe experimental data rather accurately. The agreement of experimental data with theory together with the absence of the temperature dependence for the reaction rate (which rules out its control by thermal diffusion) and with the evidence of considerable... 

The LTQ-FT mass spectrometer was introduced in late 2003 and, as expected, the main application discussed in the literature is for the analysis of proteins and peptides (Johnson et al., 2004 Syka et al., 2004). A recent book chapter (van der Greef et al., 2004) and a review article (Brown et al., 2005) discussed the application of the LTQ-FT to metabolomics. FTMS applications to dmg metabolism are still very new and dmg discovery research laboratories which have recently purchased the instmment are still in the process of developing and validating methods and approaches. A recent publication describes the depth and flexibility of the experimental setup utilizing accurate mass data-dependent exclusion MS" measurements with a LTQ-FT (Tozuka et al., 2005). We have reported several integrated approaches for determination of metabolic stability, characterization of metabolites and metabolic... 

Table 5.2 shows a representative set of accurate mass measurements of 50 pharmaceutical compounds which were acquired using an eight-scan event experiment on the LTQ-FTICR (Josephs et al., 2004b). Mass spectra from all eight scan events were acquired within 7 s, the width (at the base) of a typical chromatographic peak, as shown in Fig. 5.3 for warfarin (MW 308). The first scan event is a full-scan positive-ion MS acquired in the ion trap. If the expected protonated molecule is detected above a preset threshold, a second scan event, an ion trap (IT) data-dependent MS/MS scan, is triggered. This is followed by a third scan event, where the protonated molecule is accurately measured in the FT, and a fourth scan event, a full-scan MS/MS in the FT. 

TABLE 5.2. Accurate Mass Measurements Gathered in an 8-scan Event Data Dependant LC-MS Experiment... 

Tozuka, Z., Strupat, W. M., Shiraga, T., Ishimura, R., Hashimoto, T., Kawamura, A., and Kagayama, A. (2005). LTQ FTMS accurate mass and SRM data dependent exclusion MSn measurements for structure determination of FK228 and its metabolites. J. Mass Spectrom. Soc. Jpn. 53 89-99. 

The performance of the semiempirical methods for the calculation of thermochemical data depends on the extent to which the physics is included in the model and how well the neglected features can be accounted for by the parameterization. These methods can be assessed by validation against accurate experimental data or high level ab initio predictions. A summary of results for four semiempirical methods (MINDO/3, MNDO, AMI, and PM3) for the neutral enthalpies of formation in the G2/97 test set is given in Table 13. Overall, the newest method, PM3, does the best with an average absolute deviation of 7.02 kcal/mol. It has average absolute deviations of 3.91 and 4.27 kcal/mol for the subgroups of hydrocarbons and substituted hydrocarbons, respectively. 

The information contained in the Material Data Sheets has been compiled from data considered accurate. However, properties are known to vary depending on the source of raw materials, climatic and other variables applicable to materials of botanical origin. [Company Name] expressly disclaim any warranty expressed or implied as well as any liability for any injury or loss arising from the use of this information or the materials described. This data is not to be construed as absolutely complete since additional data may be desirable when particular conditions or circumstances exist. It is the responsibility of the user to determine the best precautions necessary for the safe handling and use of this product for their particular application. This data relates only to the specific material designated and not when used in combination with any other material. 

This is largely due to the fact that retention data depend on certain factors the effects of which are difficult to eliminate completely or control and which are normally neglected. These factors are the imperfections in the gas phase and the compressibility of the stationary phase (cf., the quantities vh v , zq and 0 in eqn. 1), the finite rate of equilibration of the solute, variations in the composition of the sorbent, spurious sorption of the solute, solubility of the carrier gas in the stationary phase, etc. Hence, even relative retention volumes and/or retention indices must depend to some extent on the kind, flow-rate and absolute pressure of the carrier gas, the load of the liquid stationary phase on the support, which production batch of the stationary phase has been used and the kind of support. The absolute column pressure will obviously vary with the column length and particle size of the support. Moreover, adjusted retention data are required in all instances, which renders it necessary to measure the dead retention time. This is a crucial step in obtaining accurate retention data and presents a problem per se. 

The technological advance that moved speleothem studies into a prominent place in the study of paleoclimates was the development of reliable and accurate methods for assigning absolute dates to individual calcite layers (Thompson et al., 1975). Such methods as U/Th dating and dating are now well established. A brief review is given here only because all of the other speleothem data depend on these techniques to establish time scales. 

Many scientists hesitate to rely on multivariate calibration models due to the complexity of the statistics involved. The quality of a multivariate model is highly dependent upon the factors chosen. Incorporation of too many factors leads to an overfit model which provides a low calibration error value, but predicts unknown samples poorly. Too few factors lead to a model that neither adequately fits the calibration data nor accurately predicts new samples. Typically, factors are included or excluded from the calibration model based upon their statistical significance, but this may not provide the opti-... 

S9 fractions. Unexpected metabolites were detected using automated MS/MS fragmentation assignment software, data-dependent methods, and accurate mass measurements in the TOF mass spectrometer. 

Lim et al. [93] investigated the use of LTQ-Orbitrap to identify human liver microsomal metabolites of carvedilol, using parent mass list triggered data-dependent multiple stage accurate mass analysis. In this study, LTQ-Orbitrap was used for accurate mass measurements at a resolving power of 60,000 to obtain mass accuracy <2 ppm for all full-scan and MS" spectra in the external calibration mode. The chemical formulas obtained from high-resolution accurate mass measurements were used to confirm structures of the product ions proposed by Mass Frontier. 

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