Triple quadrupole detectors

ML. Constanzer, C.M. Chavez-Eng, J. Dm, W.F. Kline, B.K. Matuszewski, Determination of a novel substance P inhibitor in human plasma by LC-APCI-MS detection using single and triple quadrupole detectors, J. Chromatogr. B, 807 (2004) 807. 

These applications have been reported by using the Acquity triple quadrupole detector (TQD) [28-39], the Micromass Quattro Premier triple quadrupole (QqQ) system [40], the Micromass Q-TOFII [18], and the Q-TOF Ultima [27] from Waters. As can be seen in these tandem MS equipments, two different analyzers have been reported, QqQ [28-40], the same as the two analyzers, and Q-TOF [18,27] as the hybrid system. The QqQ analyzer was the only one reported for the analysis of biological samples [30-40]. Generally, when the QqQ analyzer was used, quantification studies were performed due to their higher sensitivity in the selected ion monitoring (SRM) mode, and when the Q-TOF was used, identification or characterization was done due to its higher power for confirmation purposes. 

LC-MS tandem apparatus equipped with ESI and APCI in both PI and NI modes was evaluated [133]. This study investigated the effects of matrix interferences on the analytical performance of a triple-quadrupole detector coupled to various reversed-phase liquid chromatographic. In Table 19.8, selected LC and GC methods for assaying herbicides and fungicides in water are listed. 

In some studies the LC has been coupled to triple quadrupole and time-of-flight detectors. Moco and others (2006) used this technique to study phytochemicals including... 

Fig. 11.16. Representation of three tandem mass spectrometry (MS/MS) scan modes illustrated for a triple quadrupole instrument configuration. The top panel shows the attributes of the popular and prevalent product ion CID experiment. The first mass filter is held at a constant m/z value transmitting only ions of a single mlz value into the collision region. Conversion of a portion of translational energy into internal energy in the collision event results in excitation of the mass-selected ions, followed by unimolecular dissociation. The spectrum of product ions is recorded by scanning the second mass filter (commonly referred to as Q3 ). The center panel illustrates the precursor ion CID experiment. Ions of all mlz values are transmitted sequentially into the collision region as the first analyzer (Ql) is scanned. Only dissociation processes that generate product ions of a specific mlz ratio are transmitted by Q3 to the detector. The lower panel shows the constant neutral loss CID experiment. Both mass analyzers are scanned simultaneously, at the same rate, and at a constant mlz offset. The mlz offset is selected on the basis of known neutral elimination products (e.g., H20, NH3, CH3COOH, etc.) that may be particularly diagnostic of one or more compound classes that may be present in a sample mixture. The utility of the two compound class-specific scans (precursor ion and neutral loss) is illustrated in Fig. 11.17.

In a linear ion trap one of the most efficient ways to perform mass analysis is to eject ions radially. Hager [60] demonstrated that, by using fringe field effects, ions can also be mass-selectively ejected in the axial direction. There are several benefits for axial ejection (i) it does not require open slits in the quadrupole, (ii) the device can be operated either as a regular quadrupole or a LIT using one detector. A commercial hybrid mass spectrometer was developed based on a triple quadrupole platform where Q3 can be operated either in normal RF/DC mode or in the LIT ion trap mode (Fig. 1.24). 

In tandem MS mode, because the product ions are recorded with the same TOF mass analyzers as in full scan mode, the same high resolution and mass accuracy is obtained. Isolation of the precursor ion can be performed either at unit mass resolution or at 2-3 m/z units for multiply charged ions. Accurate mass measurements of the elemental composition of product ions greatly facilitate spectra interpretation and the main applications are peptide analysis and metabolite identification using electrospray iomzation [68]. In TOF mass analyzers accurate mass determination can be affected by various parameters such as (i) ion intensities, (ii) room temperature or (iii) detector dead time. Interestingly, the mass spectrum can be recalibrated post-acquisition using the mass of a known ion (lock mass). The lock mass can be a cluster ion in full scan mode or the residual precursor ion in the product ion mode. For LC-MS analysis a dual spray (LockSpray) source has been described, which allows the continuous introduction of a reference analyte into the mass spectrometer for improved accurate mass measurements [69]. The versatile precursor ion scan, another specific feature of the triple quadrupole, is maintained in the QqTOF instrument. However, in pre-... 

Figure 2.4 Comparison of (a) sensitivity, (b) variability, (c) selectivity, and (d) pricing between various chemical and immunological analyses for the presence of PPCPs in the environment. FID = flame ionization detector and EC = electrochemical detection. Note that GC-MS-MS can have mass detectors such as triple quadrupole and ion trap with ionization from El = electron ionization or Cl = chemical ionization, whereas LC-MS-MS with ionization from ESI = electrospray ionization, APCI = atmospheric pressure chemical ionization, or APPI = atmospheric pressure photoionization. (Adapted from Ingerslev and HaUing-Sprensen, 2003.)...

Mass spectra were recorded on a mass spectrometer (PE Sciex API III triple-quadrupole) interfaced with a Sciex Ion-Spray probe. Liquid chromatography was performed with a pump (Perkin Elmer Binary 250) and a PDA Detector (LC480 Auto Scan). The separation was achieved using a standard linear gradient (80% 2 mM ammonium acetate solution,... 

Martens-Lobenhoffer et al. [119] used chiral HPLC-atmospheric pressure photoionization tandem mass-spectrometric method for the enantio-selective quantification of omeprazole and its main metabolites in human serum. The method features solid-phase separation, normal phase chiral HPLC separation, and atmospheric pressure photoionization tandem mass spectrometry. The internal standards serve stable isotope labeled omeprazole and 5-hydroxy omeprazole. The HPLC part consists of Agilent 1100 system comprising a binary pump, an autosampler, a thermo-stated column component, and a diode array UV-VIS detector. The enantioselective chromatographic separation took place on a ReproSil Chiral-CA 5 ym 25 cm x 2 mm column, protected by a security guard system, equipped with a 4 mm x 2-mm silica filter insert. The analytes were detected by a Thermo Scientific TSQ Discovery Max triple quadrupole mass spectrometer, equipped with an APPI ion source with a... 

Figure 6.8 Diagram of instrumental configuration of the LC/MS system used for characterization of crude fermentation extracts. The system consists of the following components (1) HPLC (2) loop injector (3) guard column (4) 5pm C18 HPLC column (4.6mm x 25cm) (5) zero dead volume tee (6) UV detector (7) fraction collector (8) triple quadrupole mass spectrometer equipped with ESI interface (9) ESI power supply and gas manifold and (10) syringe pump. (Reprinted with permission from Ackermann et al., 1996a. Copyright 1996 Elsevier.)...

There are several types of ionization sources [MALDI, ESI, FAB (fast atom bombardment), PD (Cf-252 plasma desorption), El (electron ionization), Cl (chemical ionization) etc.], different types of mass analyzers [combinations of magnetic and electric sectors, quadrupolar filters (Q) and ion traps (IT), time-of-flight (TOF) and FT-ICR] and different detectors, each with its own advantages and drawbacks. We describe herein only the systems that presently have widespread use for the study of biomolecules ESI coupled to a quadrupole (or triple quadrupole, QqQ) mass analyzer or an ion trap, the MALDI source with the linear or reflectron TOF analyzer, and the FT-ICR system which can be equipped with both ESI and MALDI sources. 

Once analytes pass through the ion source, they move into the mass analyzer. The two common mass analyzers for GC are the magnetic sector and quadrupole. Also available but less common are time-of-flight (TOF), triple quadrupole, and ion trap. The purpose of all of these devices is to separate ions according to their m/z ratios. The principles behind the most common mass analyzers have been described above in the section entitled HPLC-MS and HPLC-MS/MS . The mass analyzer separates the ions, which are then sent to the detector. The most common detector is the electron multiplier, which involves... 

There are three main types of mass analyzers in ESTMS-MS instruments triple quadrupole, ion traps, and quadrupole-time-of-flight (Q-TOF). There are several differences between the mass analyzers in MALDI-TOF and in ESI-MS-MS. Unlike in MALDI-TOF-MS, in ESTMS-MS two mass analyzers are used in tandem to increase the sensitivity of the technique. The peptide ions produced by the ESI sources are carried to the first mass analyzer and only peptides of a set miz ratio are selected. The selected ions are then carried to a collision cell where they are subjected to additional fragmentation to produce smaller amino acid ions using a process called as collision induced dissociation (CID). The CID process employs inert gases such as argon for the dissociation of peptides. These smaller amino acid ions are then resolved in the second mass analyzer before sending to the detector. This process essentially enables highly sensitive detection of actual amino acid sequence of the peptides based on the mIz ratios of individual amino acids. 

Figure 15.7. Typical configurations used in biological MS. In MALDI-TOF, the ions produced by a short laser pulse travel across a flight tube, arriving at different times at the detector. In ESI-triple quadrupole, the first quadrupole (Ql) is used to separate the sprayed ions, in the second (Q2, also called the fragmentation cell) argon atoms collide with the ions the resulting ions (daughter ions) are analyzed in Q3, and subsequently detected.

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