Mass spectrometry triple quadrupole methods

Tandem mass spectrometry (MS/MS) is a method for obtaining sequence and structural information by measurement of the mass-to-charge ratios of ionized molecules before and after dissociation reactions within a mass spectrometer which consists essentially of two mass spectrometers in tandem. In the first step, precursor ions are selected for further fragmentation by energy impact and interaction with a collision gas. The generated product ions can be analyzed by a second scan step. MS/MS measurements of peptides can be performed using electrospray or matrix-assisted laser desorption/ionization in combination with triple quadruple, ion trap, quadrupole-TOF (time-of-flight), TOF-TOF or ion cyclotron resonance MS. Tandem... 

A further extension of the DFG S19 method was achieved when polar analytes and those unsuitable for GC were determined by LC/MS or more preferably by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Triple-quadrupole MS/MS and ion trap MS" have become more affordable and acceptable in the recent past. These techniques provide multiple analyte methods by employing modes such as time segments, scan events or multiple injections. By improving the selectivity and sensitivity of detection after HPLC separation, the DFG S19 extraction and cleanup scheme can be applied to polar or high molecular weight analytes, and cleanup steps such as Si02 fractionation or even GPC become unnecessary. 

Stenhoff et al. [117] determined enantiomers of omeprazole in blood plasma by normal-phase liquid chromatography and detection by atmospheric-pressure ionization tandem mass spectrometry. The enantioselec-tive assay of omeprazole is using normal-phase liquid chromatography on a Chiralpak AD column and detection by mass spectrometry. Omeprazole is extracted by a mixture of dichloromethane and hexane and, after evaporation, redissolution and injection, separated into its enantiomers on the chiral stationary phase. Detection is made by a triple quadrupole mass spectrometer, using deuterated analogs and internal standards. The method enables determination in plasma down to 10 nmol/1 and shows excellent consistency suited for pharmacokinetic studies in man. 

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... 

At about the same time, our laboratory has reported the development and validation of an LC tandem MS assay for as much as six TKIs simultaneously. The proposed LC-MS/MS method allows the simultaneous determination of clinically relevant ranges of concentrations for the six major TKIs currently in use imatinib, dasatinib, nilotinib, sunitinib, sorafenib, and lapatinib [122], Plasma is purified by acetonitrile protein precipitation followed by reversed-phase chromatographic separation. Analyte quantification is performed by electrospray ionization-triple quadrupole mass spectrometry by selected reaction monitoring (SRM) detection using the positive mode. This was the first broad-range LC-MS/MS assay covering the major currently in-use TKIs. 

Fig. 5 Statistical evaluation of LC-MS-based methods for tropane alkaloids referred in this chapter. (a) Relative frequency of ionization methods. +APCI positive atmospheric pressure chemical ionization, +ESI positive electrospray ionization, FAB fast atom bombardment, +TSP positive thermospray, (b) Relative frequency of scan modes used. MS full scan MS, MS/MS tandem mass spectrometry (product ion scan), MRM multiple reaction monitoring, SIM selected ion monitoring, (c) Relative frequency of mass analysers used. EBQtQ2 double focusing sector field mass spectrometer, IT ion trap, QqQ triple quadrupole, SQ single quadrupole. Considered publications were found by PubMed data-based search and references cited in these articles...

Golge, O., Kabak, B. Evaluation of QuEChERS sample preparation and liquid chromatography-triple-quadrupole mass spectrometry method for the determination of 109 pesticide residues in tomatoes. Food Chem. 176, 319-332 (2015)... 

The identity of the defined peptides was confirmed by electrospray mass spectrometry [13,62] and the purity of defined peptides was higher than 80% as determined by HPLC. The amino acid composition of selected peptide libraries and of the sublibraries was determined by pool sequencing [14] (Fig. 11.1) and amino acid analysis. Deviations from equimolar representation of the amino acids in randomized sequence positions were found to be within the error limits of the analytical methods [12]. Electrospray mass spectrometry for pattern analysis of peptide libraries differing in the position of the defined amino acid was carried out with a triple quadrupole mass spectrometer (Fisons, Manchester, UK) (Fig. 11.2). 

The ESI and APCI are both soft ionization techniques, hence the spectra obtained using these methods are usually very simple and consist predominantly of the pseudomolecular ion. When more information is required, tandem mass spectrometry is a popular option. Several different types of tandem LC/MS systems can be found, with triple quadrupole and ion trap being the most popular choices. Hybrid systems including magnetic sector-quadmpole, magnetic sector-TOF, quadrupole-TOF (Q-TOF) and ion trap-TOF have been described. The most successful among these hybrids is the Q-TOF instrument. 

As for gas chromatography coupling systems, tandem mass spectrometry is now the method of choice for identification and quantitation purposes of herbicides, with ion trap or triple-quadrupole based Although triple quadrupole MS/MS is more sensitive... 

Johnson reported at the 59th TSRC, in 2005, on the results of the identification of spin-trapped vapor-phase free radicals in MSS via an ESI-triple quadrupole tandem mass spectrometry analysis method. Four alkoxyl free radicals were unequivocally identified (OC2H5, OC3H7, OC4H9, and OCjHjj). The superoxide free radical was also tentatively identified (27A56). 

Shevchenko, A., I. Chemushevich, et al., 2000, De Novo peptide sequencing by nanoelectrospray tandem mass spectrometry using triple quadmpole and quadrupole/time-of-flight instruments. Methods Mol. Biol. 146 1-16. 

Corn-based foods followed by fumonisin B2 (FB2).The problems and risks associated with fumonisin contamination have resulted in the development of precise, reliable and sensitive methods for its determination in corn and corn-based foods (Magan Olsen, 2004, as cited in Silva et al., 2009). Therefore, the quality parameters in the analysis of FBI and FB2 in corn-based products obtained with LC with fluorescence detector have been investigated (Silva et al, 2009). Furthermore, a comparison study between fluorescence detector (FD), mass spectrometry, and tandem mass spectrometry with a triple quadrupole (QqQ) analyzer using an electrospray ionization interface for the determination of fumonisin B1 and B2 in corn-based products has been performed. A comparative study of the three LC detectors, FD, single quadrupole, QqQ for the analysis of fumonisins in corn samples has been performed. The response achieved by the three detectors was sensitive enough to study the maximum contents established by the EU legislation. These LC detectors would be appropriate for quantification purposes but the acquisition of at least two transitions achieved with QqQ provided a univocal identification. 

---