Identification Using Data-Dependent Analysis

Impurity Identification Using Data-Dependent Analysis 

Regulatory authorities strictly scrutinize the leachables (e.g., plasticizers, impurities) that may come from medical devices and drugs. It is the responsibility of the drug or medical device company to identify the leachables and to provide adequate testing of their toxicity. Monitoring methods must be developed and validated to effectively control toxic leachables during the manufacture of high quality pharmaceuticals. 

As a result, materials for medical devices and drug products must be tested for leachable components. Once a known toxic compound is discovered, it must be identified for the assessment of toxicity, followed by the monitoring of levels using validated methods as required by the FDA. This identification procedure could be a time-consuming process with traditional methods that are based on fractionation and individual component analysis. 

In the Tiller study, adhesive was applied to a glass bottle and cured. Highly purified water was placed over the adhesive, heated at 50 °C for 3 days, and analyzed with gradient reversed-phase HPLC. An LC/ITMS with ESI was used to profile the polyesters in the adhesive extracts with full-scan mass spectra and corresponding product ion spectra triggered by an ion abundance that surpassed a threshold. 

Similar to previous structure identification methods described for metabolites, impurities, and degradants, the knowledge of the physiological or chemical process, in this case the adhesive synthesis process, helped in the rapid interpretation of the MS/MS spectra of the unknown components. No user input about the sample composition is needed for the data-dependent analysis scheme thus, these experiments are simple and rapid to perform. The result is a fairly routine approach to structural screening of unknown mixtures during the manufacturing stage. 

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Impurity Identification Using Data-Dependent Analysis... 

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. 

For a same molecular ratio of aqueous NaY solutions (Y = OH, Cl), experimental data underlines specific effects of nascent OH radicals on transient UV and near-IR electronic configurations. Complex investigations of PHET reactions in the polarization CTTS well of aqueous CT and OH ions are in progress. We should wonder whether a change in the size of ionic radius (OH -1.76 A vs Cl" 2.35 A) or in the separation of the energy levels influence early branchings of ultrafast electronic trajectories. A key point of these studies is that the spectroscopic predictions of computed model-dependent analysis are compared to a direct identification of transient spectral bands, using a cooled Optical Multichannel Analyzer... 

The rapid structure identification of metabolites is a powerful complement to previously described quantitative approaches. The utility of an automated metabolite identification approach, using LC/MS/MS with an ion trap mass spectrometer has been demon-strated.f In this study, MS" analysis is automated to provide maximum structural information in combination with predictive strategies for biotransformation. Automated data-dependent scan functions are used to generate full scan, MS/MS, and MS" mass spectra of... 

Gu and Lim [76] described the use of DDA for microsomal stability studies and metabolite profiling. First, the relevant m/z of an unknown lead compounds is determined. This information is used in SIM experiments for quantitation. Once the peak area of the compoimd tested falls below a certain threshold, e.g., 60% of the initial value, data-dependent product-ion MS-MS analysis is performed for metabolite identification. Some results for adatanserin are shown in Figure 10.11. 

It has been demonstrated also that the iTRAQ tandem mass spectrometric quantitative analysis strategy can be used in conjunction with the quadrupole ion trap by performing multiple stages of mass analysis (that is, MS ) [125], For example, chemical derivatization with the iTRAQ reagent not only labels the N-terminus of a peptide, but the lysine side chain also. Thus, tryptic peptides with a modified lysine residue present at the C-terminus will produce a yj product ion at m/z 291 following ClD-tandem mass spectrometry. To generate the low m/z iTRAQ reporter ions required for quantitation, the yj product ion is isolated and subjected to data-dependent CID-MS. Using this approach, peptide identification is achieved in the MS/MS scan, while quantitation is achieved via MS. ... 

However, an alternative method of SIM is still commonly used in lipidomics, particularly in the platforms associated with LC-MS, where high duty cycle instruments such as Q-ToF-type mass spectrometers are employed. In this case, a product-ion analysis at any moment of elution time could be performed for certain ions above a preset threshold for identification of these species (i.e., data-dependent acquisition), while a mass spectrum in the full MS mode, which detects both miz values and intensities of the ions between the mass ranges of intoest at the eluent time, is acquired over the entire elution time period for quantification. Owing to the very high scan rate, high sensitivity, and very fast and efficient acquisition of full product-ion mass spectra with the Q-ToF-type instruments over QqQ-type mass spectrometers, multiple acquisitions can be recorded at an elution time for identification of the relatively abundant species. The combination of elution time, m/z value, and a number of product-ion mass spectra provides reasonably accurate information about the chemistry of lipid species. 

To achieve identification of the quantified species, an approach with data-dependent product-ion analysis would be useful. However, an increased duty cycle of the instrument employed is required as the number of the analyzing lipids is increased. Alternatively, a high mass accuracy/resolution mass spectrometer would help to resolve the isobaric molecular ions from different lipid classes although isomeric species resulting from the regiospecificity and/or the double-bond location still cannot be resolved. 

First, a distinction can be made between non-parametric and parametric identification. Non-parametric system identification involves the estimation of an impulse response function, frequency response function (FRF), correlation function, or power spectral density (PSD), not as a mathematical function depending on a few parameters, but as a set of tabulated values for each considered time lag or frequency. Although nonparametric models are sometimes directly used for modal analysis, they are most often used as preprocessed data for parametric identification since the estimation accuracy of parametric approaches is much higher than that of nonparametric approaches (Peeters and De Roeck 2001 Reynders 2012). 

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