Information-dependent acquisition

Data-dependent acquisition ability has been developed and incorporated into most software packages [MetaboLynx, Xcalibur, and Analyst Information Dependent Acquisition (IDA)]. In data-dependent acquisition mode, a mass spectrometer decides on the fly whether to collect MS/MS or MSn data, remain in full scan MS mode, or conduct other survey scans based upon user-defined criteria. Product ion spectra of potential metabolites can be automatically acquired in a single LC/ MS run. However, false positives may be generated due to highly intense matrix ion signals that may inadvertently trigger MS/MS or MSn scan functions. 

To be able to use MS/MS spectra library searching for general unknown screening, it is necessary to use an automatic process, called data dependent acquisition or information-dependent acquisition, to select the parent ions of interest, totally unexpected by definition, and to dissociate them and monitor their fragments. 

Li, A. C. Alton, D. Bryant, M. S. Shou, W. Z. Simultaneously quantifying parent drugs and screening for metabolites in plasma pharmacokinetic samples using selected reaction monitoring information-dependent acquisition on a QTrap instrument. Rupid Commun Mass Spectrom 2005, 19, 1943-1950. 

Alternative to DDA, the term information-dependent acquisition (IDA) is used. Both DDA and IDA describe an automatic mode where the MS/MS parameters are collected automatically by calculating the parameter set (e.g., collision energy) based on the mass and charge state of the selected precursor ion. 

Data-dependent acqnisition (DDA) is a mode of operation, where the MS experiment performed in a particular scan is based on the data acqnired in a previons scan. In a simple form, a DDA experiment switches the instrument from full-scan MS acquisition to full-scan product-ion MS-MS when the total-ion intensity or a selected-ion intensity exceeds a preset threshold. This avoids the need to perform two consecutive injections for the identification of unknowns in a mixture first to obtain the m/z values for the intact protonated molecules of the unknowns, and second to acquire the product-ion MS-MS spectra of these unknowns in a time-scheduled procedure, switching between various preselected precursor ions as a function of the chromatographic retention time. The DDA was promoted by Thermo Finnigan upon the introduction of the API-ion trap combinations [44-46]. Similar procedures are available for other commercial ion-trap systems, as well as for triple-quadrupoles, e.g.. Information Dependent Acquisition (IDA) from Applied Biosystems MDS Sciex, Data-directed Analysis (DDA) from Waters, and Smart Select from Bruker. 

Data-dependent switching between a survey-MS mode and the product-ion MS-MS mode (Ch. 2.4.2) in the LC-MS analysis of tryptic digest on a triple-quadrapole instrument was pioneered by Stahl et al. [140]. The MS-MS spectra obtained were correlated wiA a protein sequence database by using the SEQUEST program. DDA (also called SmartSelect, or Information-Dependent Acquisition, IDA) on ion-trap, Q-LIT, and Q-TOF instruments have become important tools in high-throughput protein characterization. 

Le Blanc, Y.C.Y Bloomfield, N. Dynamic Background Subtraction to Improve Candidate Ion Selection for Information Dependant Acquisition LC-MS/MS Analysis, in Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics, Nashville, TN, May 23-27, 2004. 

To improve upon the approach employed by King et al. [164], Li et al. [327] used SRM-triggered information-dependent acquisition (IDA) to acquire both parent drug quantification data and qualitative metabolite MS/MS data. To validate the IDA approach, Li et al. [327] tested both the conventional triple quadrupole mode as well as in the ion trap mode and showed that the cycle time improved from 2.78 to 1.14 s with the IDA approach. The longer cycle time in the triple quadrupole mode of operation would have resulted in possibly missing some the metabolites. 

LC-ESI-MS/MS analysis. To examine the potential PTM of a protein after MADLI-TOF mass, a liquid chromatography-tandom mass spectrometry (LC-ESI-MS/MS) is run to obtain information-dependent acquisition (IDA) data. Alternatively, an LC-ESI-MS/MS analysis can be performed without prior MALDI-TOF. However, it is the most common practice to first conduct a MALDI-TOF mass to determine the amount of sample to be loaded on a subsequent LC-ESI-MS/MS. The IDA data could then be searched at Mascot MS/MS data search (available online at http //www.matrixscience.com/) by selecting several parameters, such as protein data bank (i.e., NCBI and MSDB), the species, the fixed modification (i.e., carbamidomethyl cystein), the variable modifications, and the mass tolerance. The search result will generate information about the protein. The reconstructed MS/MS spectrum along with the calculated mass value of product ions matched in the original MS/MS spectrum can be obtained, which will show the residue modified by PTM. To confirm the modification, manual analysis of the MS/MS data is essential. 

Tryptic digests of RIP140 protein was subjected to LC-ESI-MS/MS. Three independent full-scan ion chromatograms from m/z 400-550, 550-750, and 750-1200 were recorded in an information-dependent acquisition (IDA) mode to acquire MS/MS data. The IDA data were searched online at MASCOT (http //www.matrixscience.com) MS/MS data search at the NCBI data bank. The MS/MS data were analyzed manually to confirm the sequence of the modified and the unmodified forms of the same peptide identified by the data bank search. The full scan chromatograms were analyzed to assign the charged state, retention time, and intensities of the peptides. 

Sierra Analytics and Applied Biosystems investigated the metabolic profile of indinavir, an HIV protease inhibitor with a very short half-life (2 hours), readily metabolised via CYPs to produce phase I and subsequent II products. Aliquots (10 pL) of indinavir incubated with rat liver S9 fractions were separated by online liquid chromatography and analysed with an Applied Biosystems hybrid triple quadrupole/linear ion trap mass spectrometer in information dependent acquisition (IDA) mode. This consisted of an enhanced MS survey scan followed by enhanced product ion scans for the two most intense parent ions as dependent MS/MS experiments. 

Bloomfield, N. Mass defect triggered information dependent acquisition. MDS Sdex, Can. and Applera Corporation, is avaUable at http //www.wipo.int/pctdb/en/wo.jsp WO=2007076606, 2007. 

Recently introduced hybrid triple quadruple—linear ion trap (QTRAP) mass spectrometer has scan functions identical to those of classical triple quadruple (PI scan, NL scan, and MRM). It can be used for small-molecule quantification with MRM in both bioanalysis and in vitro ADME studies (Hopfgartner et ah, 2004). The QTRAP also has scan functions (full MS scan and MS/MS scan) similar to an ion trap mass spectrometer. Most importantly, MS, MRM, PI, and NL scans on QTRAP instruments can serve as survey scans to trigger the information-dependent acquisition (IDA) of enhanced product ion spectra (EPI) with polarity switching, which provide product ion spectra with rich fragments with no low-mass cutoff (Xia et al., 2003 Zheng et al., 2007 Wen et al., 2008b Yao et al., 2008 Jian et al., 2009). The information-dependent acquisitions have been widely applied to reactive... 

Politi L, Morini L, Polettini A. A direct screening procedure for diuretics in human urine by liquid chromatography—tandem mass spectrometry with information dependent acquisition. Clin Chim Acta 2007 386 46-52. 

A QqQtiap mass spectrometer (Section 6.4.6) was used in conventional triple quadrupole MRM mode for routine quantitation, but in some experiments this was combined using the information dependent acquisition (IDA) software facility function with the ion trap function for identification of unknowns and/or confirmation of target analytes. Only one MRM transition was monitored for each analyte, thus gaining only 2.5 identification points rather than the specified three (European Commission 2002, see Table 9.1) this was undoubtedly a consequence of the large number of analytes monitored in this multiresidue analysis. A retention time within 5 % of the standard value determined for pure analytes in distilled water was also a required criterion (Hua 2006) for confirmation of identity. 

Figure 11.33 (a) Comparison of concentration vs time profiles of compounds A and B acquired using the QTrap in conventional triple quadmpole MRM mode ( SRM Only ) with those acquired in survey mode in which the conventional MRM acquisition for the parent compound was combined with MRM-triggered information dependent acquisition of enhanced full scan fragment ion spectra (Q3 operated in linear trap mode) for metabolites predicted to be present on the basis of known metabolic pathways, (b) Peak area vs time profiles of metabolites of compounds A and B based on data acquired in the survey experiments (see Figure 11.34). Reproduced from Li, Rapid Commun. Mass Spectrom. 19, 1943 (2005), with permission of John Wiley Sons Ltd.

Improvement with respect to these SRM methods was rendered possible by the availability of data-dependent acquisition or information-dependent acquisition (IDA), by which a tandem mass spectrometer can automatically switch from a survey mode to a dependent (or confirmation), full-spectrum MS/MS mode. In addition, the introduction of linear ion-trap-triple quadrupole (LIT-QqQ) hybrid instruments further extended the possibilities of LC-MS/MS in STA or GUS. In this instrument, the second mass analyzer can be used as either a conventional quadrupole mass analyzer or a linear ion trap, which by accumulation of ions provides enhanced full-spectrum sensitivity compared to a conventional quadrupole. The group of Weinmann used targeted SRM with up to 700 transitions as the survey detection mode, and the enhanced product ion (EPI) spectrum mode as the dependent mode (11). Whereas this procedure seems to be a more specific approach to STA as it allows searching rich spectra against those entered in libraries, the use of SRM as the survey mode cannot answer the more general clinical question as to whether an individual has been intoxicated at all, rather than intoxicated with a compound from a predefined list (12). Also, the use of only the positive-ion mode narrows the detection window. 

It should be noted that as the development of mass spectrometers possessing a high duty cycle sueh as SCIEX TripleTOF 5600 system, which shows a 100-Hz acquisition speed, conducting product-ion analysis of all the ions in a mass range of interest unit by unit or information-dependent acquisition becomes feasible. Alternatively, when an ultra-mass accuracy/resolution instrument such as the Orbitrap Fusion (Lumos) Tribrid mass spectrometer from Thermo Fisher Scientific... 

Increasingly, tandem full-scanning instruments are being operated in information-dependent acquisition (IDA—MS/MS) mode. This duty... 

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