Triple quadrupole mass spectrometers sensitivity

A triple-quadrupole mass spectrometer with an electrospray interface is recommended for achieving the best sensitivity and selectivity in the quantitative determination of sulfonylurea herbicides. Ion trap mass spectrometers may also be used, but reduced sensitivity may be observed, in addition to more severe matrix suppression due to the increased need for sample concentration or to the space charge effect. Also, we have observed that two parent to daughter transitions cannot be obtained for some of the sulfonylurea compounds when ion traps are used in the MS/MS mode. Most electrospray LC/MS and LC/MS/MS analyses of sulfonylureas have been done in the positive ion mode with acidic HPLC mobile phases. The formation of (M - - H)+ ions in solution and in the gas phase under these conditions is favorable, and fragmentation or formation of undesirable adducts can easily be minimized. Owing to the acid-base nature of these molecules, negative ionization can also be used, with the formation of (M - H) ions at mobile phase pH values of approximately 5-7, but the sensitivity is often reduced as compared with the positive ion mode. 

For HPLC/MS/MS analysis, a triple-quadrupole mass spectrometer with an electrospray interface is recommended for achieving the best sensitivity and speciflcity in the quantitative determination of oxime carbamates and their metabolites. This allows... 

Currently, HPLC/fiuorescence is still the most common technique for the determination of residues of oxime carbamates. With the introduction of ESI and APCI MS interfaces, HPLC/MS analysis for oxime carbamates in various sample matrices has become widespread. However, for a rapid, sensitive, and specific analysis of biological and environmental samples, HPLC/MS/MS is preferred to HPLC/MS and HPLC/fiuorescence. With time, improved and affordable triple-quadrupole mass spectrometers will be available in more analytical laboratories. With stricter regulatory requirements, e.g., highly specific and conclusive methods with lower LOQ, HPLC/MS/MS will be a method of choice for oxime carbamates and their metabolites. 

FTIR in multiply hyphenated systems may be either off-line (with on-line collection of peaks) [666,667] or directly on-line [668,669]. Off-line techniques may be essential for minor components in a mixture, where long analysis times are required for FT-based techniques (NMR, IR), or where careful optimisation of the response is needed. In an early study a prototype configuration comprised SEC, a triple quadrupole mass spectrometer, off-line evaporative FTIR with splitting after UV detection see Scheme 7.12c [667]. Off-line IR spectroscopy (LC Transform ) provides good-quality spectra with no interferences from the mobile phase and the potential for very high sensitivity. Advanced approaches consist of an HPLC system incorporating a UV diode array, FTIR (using an ATR flow-cell to obtain on-flow IR spectra), NMR and ToF-MS. 

Figeys, D. Aebersold, R. High sensitivity identification of proteins by electrospray ionization tandem mass spectrometry inital comparison between an ion trap mass spectrometer and a triple quadrupole mass spectrometer. Electrophoresis 1997,18, 360-368. 

MS vendors continue to improve their triple quadrupole mass spectrometers. Typically, the latest models of these MS/MS systems are more sensitive than previous systems and scan faster than the... 

Triple quadrupole mass spectrometers, QqQ, have almost become a standard analytical tool for LC-MS/MS applications, in particular when accurate quantitation is desired (Chap. 12). Ever since their introduction [124-126] they have continuously been improved in terms of mass range, resolution, and sensitivity (Fig. 4.38). [127-129]... 

Yinon et al. (228) used an HPLC interfaced with a triple-quadrupole mass spectrometer by means of a particle beam for the identification of several azo dyes. Characterization of the dyes was achieved by observing typical fragment ions formed by cleavage of the N-C and C-N bond on either side of the azo linkage and/or cleavage of the N=N double bond with the transfer of two hydrogen atoms to form an amine. Sensitivity was observed to be two to three orders of magnitude worse than with thermospray ionization. 

Hughes, N., Winnik, W., Dunyach, J. J., Amad, M., Splendore, M., and Paul, G. (2003). High-sensitivity quantitation of cabergoline and pergolide using a triple-quadrupole mass spectrometer with enhanced mass-resolution capabilities. J. Mass Spectrom. 38 743-751. 

Both of the above examples illustrate that the sensitivity of the MDF method, in general, is comparable to PIS analysis and better than NLS methods (Figs 6.9 and 6.10). The sensitivity of the MDF method is attributed at least in part to the full-scan capability of high-resolution mass spectrometers such as the Q-TOF and LTQ-FTICR, which could be several times more sensitive than full-scan analysis by a triple-quadrupole mass spectrometer (Kostiainen et al., 2003). 

The mass spectrometer used by Banner and colleagues was a rapid scanning magnetic sector instrument that easily provided a resolution of one mass unit. Nowadays, mass spectrometers (giving vastly improved resolution) are mostly used with capillary columns and operated in a very similar manner, with the column eluent passing directly into the ionization source of the spectrometer. The most advanced system involves the triple quadrupole mass spectrometer, which gives extremely impressive in-line sensitivity, selectivity and resolution. 

Electrospray mass spectra were recorded on a Perkin-Elmer Sciex API-Ill triple quadrupole mass spectrometer (Thornhill, Canada) with general MS and LC setup as previously described (5-8). Modifications of the instrument which improve sensitivity for negative-ion mode detection of phosphorylation and sulfation have also been described before (7,8). Because phosphorylated or sulfated peptides produce predominantly negatively charged marker ions while glycosylation or acylation yield positively charged species, these two classes of modification cannot both be detected in a single LCMS experiment. 

If the same sample is characterized by SIM, a clear improvement in selectivity and sensitivity is observed (see Fig. 13d). All spectral information on the peak is sacrificed as the instrument is configured to monitor only a single m/g window. Additional selectivity is obtained by monitoring an MRM transition, in this case on a triple quadrupole mass spectrometer (see Fig. 13e). The precursor ion of gabapentin, (M + FI)1+ 172 m/ 7y, is selected in Ql and fragmented in the collision cell, and the product ion, (M + FI)1+ 154 m/g, is monitored by Q3. This technique provides the highest combination of selectivity and signal to noise (S/N) with the sacrifice of qualitative information. 

While a typical standard curve for a discovery PK study would still be in the 1-10,000 ng/mL range, it is becoming more likely that one would need an assay in the 0.1-1000 ng/mL range. The reason is that test compounds are becoming more potent so that lower doses are being given (in some cases) to test animals in various efficacy assays. As stated above, this has not been an issue for the bioanalytical community because the triple quadrupole mass spectrometers have become more sensitive. 

Triple quadrupole mass spectrometers can perform tandem mass scan experiments in various modes including product ion (MS/MS), precursor ion, and neutral loss scan and SRM experiments, but they cannot be used for sequential MS" experiments. The high sensitivity and specificity, in the SRM mode, have made triple quadrupole mass spectrometers a logical choice for metabolic stability experiments performed at relevant substrate concentrations. Despite the sensitivity of the triple quadrupole mass spectrometers, when an NCE or an NCE series exhibit unacceptable PK properties, metabolite identification studies are often initiated as follow-up studies in a separate set of experiments using incubation concentrations higher than the Km of an NCE. Incubations at higher concentrations are required because conventional metabolite identification experiments required operation of the triple quadrupole mass spectrometer in the full-scan mode, which results in poor duty cycle and diminished sensitivity [287,288],... 

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