On the inter‐instrument and the inter‐laboratory transferability of a tandem mass spectral reference library. 3. Focus on ion trap and upfront CID

Abstract

Mass spectral libraries represent versatile tools for the identification of small bioorganic molecules. Libraries based on electron impact spectra are rated robust and transferable. Tandem mass spectral libraries are often considered to work properly only on the instrument that has been used to build the library. An exception from that rule is the 'Wiley Registry of Tandem Mass Spectral Data, MSforID'. In various studies with data sets from different kinds of tandem mass spectrometric instruments, the outstanding sensitivity and robustness of this tandem mass spectral library search approach was demonstrated. The instrumental platforms tested, however, mainly included various tandem-in-space instruments. Herein, the results of a multicenter study with a focus on upfront and tandem-in-time fragmentation are presented. Five laboratories participated and provided fragment ion mass spectra from the following types of mass spectrometers: time-of-flight (TOF), quadrupole-hexapole-TOF, linear ion trap (LIT), 3-D ion trap and LIT-Orbitrap. A total number of 1231 fragment ion mass spectra were collected from 20 test compounds (amiloride, buphenin, cinchocaine, cyclizine, desipramine, dihydroergotamine, dyxirazine, dosulepin, ergotamine, ethambutol, etofylline, mefruside, metoclopramide, phenazone, phentermine, phenytoin, sulfamethoxazole, sulfamoxole, sulthiame and tetracycline) on seven electrospray ionization instruments using 18 different instrumental configurations for fragmentation. For 1222 spectra (99.3%), the correct compound was retrieved as the best matching compound. Classified matches (matches with 'relative average match probability' >40.0) were obtained for 1207 spectra (98.1%). This high percentage of correct identifications clearly supports the hypothesis that the tandem mass spectral library approach tested is a robust and universal identification tool.

Analytical Validation of a Portable Mass Spectrometer Featuring Interchangeable, Ambient Ionization Sources for High Throughput Forensic Evidence Screening

“…Ion trap instrumentation is known to produce a low number of compound-specific fragments, as resonant excitationcollision induced dissociation (CID) commonly produces product ions too cool to undergo further fragmentation and lowmass fragment ions are inefficiently trapped [66]. The combination of inter-analyzer differences, variable CID energies and a low number of compound-specific transitions has been shown to hinder accurate identification via library searching [67], which led to the misidentification of 25I-NBOMe.…”

“…It has been asserted that the addition of the N-(2-methoxy)benzyl group to the 2C-phenethylamine structure (another electron donating aromatic ring, as seen in Supplementary Figure S-8C) creates more favorable sites for dissociation that can occur along the -C-C-N-C-linkage chain, specifically C-C bond cleavage between the α-and β-carbon atoms on the ethylene bridge [68,69]. The complexity and intensity to which these fragmentation patterns are seen is highly dependent on the MS/MS conditions utilized [44], which leads to the inter-instrument variations reported [66,70]. While NBOMe derivatives may represent a special case due to the number of low abundance transitions seen, instrument-specific spectral databases [71] may be more prudent in scenarios where automated chemical identification is needed, but variability is a concern.…”

Post-acquisition data processing for the screening of transformation products of different organic contaminants. Two-year monitoring of river water using LC-ESI-QTOF-MS and GCxGC-EI-TOF-MS

“…METLIN is a metabolite database principally (but not only) for metabolomics approaches, containing over 64,000 structures (pharmaceuticals, some of their metabolites, pesticides, human and animal endogenous compounds, polyphenols and plant metabolites, etc.). It incorporates more than 59,000 high-resolution MS/MS spectra at different CEs (Oberacher et al 2012;Tautenhahn et al 2012;Oberacher et al 2009). …”

Applying Tandem Mass Spectral Libraries for Solving the Critical Assessment of Small Molecule Identification (CASMI) LC/MS Challenge 2012

“…State-of-the-art libraries are considered to allow sensitive, specific and robust compound identification [6,14,15,16]. Typically, advanced library structures (e.g., comprehensive coverage of compound-specific breakdown curves with reference spectra acquired at different collision energy (CE) settings) and tailor-made search algorithms are combined to create efficient tools for compound identification.…”

“…The library comes bundled with a tailor-made search algorithm (MSforID Search). The Wiley Registry MS/MS was extensively tested [6,7,14,15,16]. The results of multicentre and cross-validation studies clearly suggest that the Wiley Registry MS/MS allows reliable and robust identification with data acquired on various instruments.…”