Triple Quadrupole Mass Spectrometry (triple + quadrupole_mass_spectrometry)

Distribution by Scientific Domains


Selected Abstracts


Structure elucidation of aplidine metabolites formed in vitro by human liver microsomes using triple quadrupole mass spectrometry

JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 6 2005
Esther F. A. Brandon
Abstract The cyclic depsipeptide aplidine is a new anti-cancer drug of marine origin. Four metabolites of this compound were found after incubation with pooled human microsomes using gradient high-performance liquid chromatography with ultraviolet detection. After chromatographic isolation, the metabolites have been identified using nano-electrospray triple quadrupole mass spectrometry. A highly specific sodium-ion interaction with the cyclic structure opens the depsipeptide ring, and cleavage of the amino acid residues gives sequence information when activated by collision-induced dissociation in the second quadrupole. The aplidine molecule could undergo the following metabolic reactions: hydroxylation at the isopropyl group (metabolites apli-h 1 and apli-h 2); C-dealkylation at the N(Me)-leucine group (metabolite apli-da); hydroxylation at the isopropyl group and C-dealkylation at the N(Me)-leucine group (metabolite apli-da/h), and C-demethylation at the threonine group (metabolite apli-dm). The identification of these metabolites formed in vitro may greatly aid the elucidation of the metabolic pathways of aplidine in humans. Copyright 2005 John Wiley & Sons, Ltd. [source]


Comparison of triple quadrupole, hybrid linear ion trap triple quadrupole, time-of-flight and LTQ-Orbitrap mass spectrometers in drug discovery phase metabolite screening and identification in vitro , amitriptyline and verapamil as model compounds

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 7 2010
Timo Rousu
Liquid chromatography in combination with mass spectrometry (LC/MS) is a superior analytical technique for metabolite profiling and identification studies performed in drug discovery and development laboratories. In the early phase of drug discovery the analytical approach should be both time- and cost-effective, thus providing as much data as possible with only one visit to the laboratory, without the need for further experiments. Recent developments in mass spectrometers have created a situation where many different mass spectrometers are available for the task, each with their specific strengths and drawbacks. We compared the metabolite screening properties of four main types of mass spectrometers used in analytical laboratories, considering both the ability to detect the metabolites and provide structural information, as well as the issues related to time consumption in laboratory and thereafter in data processing. Human liver microsomal incubations with amitriptyline and verapamil were used as test samples, and early-phase ,one lab visit only' approaches were used with all instruments. In total, 28 amitriptyline and 69 verapamil metabolites were found and tentatively identified. Time-of-flight mass spectrometry (TOFMS) was the only approach detecting all of them, shown to be the most suitable instrument for elucidating as comprehensive metabolite profile as possible leading also to lowest overall time consumption together with the LTQ-Orbitrap approach. The latter however suffered from lower detection sensitivity and false negatives, and due to slow data acquisition rate required slower chromatography. Approaches with triple quadrupole mass spectrometry (QqQ) and hybrid linear ion trap triple quadrupole mass spectrometry (Q-Trap) provided the highest amount of fragment ion data for structural elucidation, but, in addition to being unable to produce very high-important accurate mass data, they suffered from many false negatives, and especially with the QqQ, from very high overall time consumption. Copyright 2010 John Wiley & Sons, Ltd. [source]


Development and validation of a liquid chromatography/tandem mass spectrometric method for the determination of 39 mycotoxins in wheat and maize

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2006
Michael Sulyok
This paper describes the first validated method for the determination of 39 mycotoxins in wheat and maize using a single extraction step followed by liquid chromatography with electrospray ionization triple quadrupole mass spectrometry (LC/ESI-MS/MS) without the need for any clean-up. The 39 analytes included A- and B-trichothecenes (including deoxynivalenol-3-glucoside), zearalenone and related derivatives, fumonisins, enniatins, ergot alkaloids, ochratoxins, aflatoxins and moniliformin. The large number and the chemical diversity of the analytes required the application of the positive as well as the negative ion ESI mode in two consecutive chromatographic runs of 21,min each. The solvent mixture acetonitrile/water/acetic acid 79,+,20,+,1 (v/v/v) has been determined as the best compromise for the extraction of the analytes from wheat and maize. Raw extracts were diluted 1,+,1 and were injected without any clean-up. Ion-suppression effects due to co-eluting matrix components were negligible in the case of wheat, whereas significant signal suppression for 12 analytes was observed in maize, causing purely proportional systematic errors. Method performance characteristics were determined after spiking blank samples on multiple levels in triplicate. Coefficients of variation of the overall process of <5.1% and <3.0% were obtained for wheat and maize, respectively, from linear calibration data. Limits of detection ranged from 0.03 to 220,g/kg. Apparent recoveries (including both the recoveries of the extraction step and matrix effects) were within the range of 100,,10% for approximately half of the analytes. In extreme cases the apparent recoveries dropped to about 20%, but this could be compensated for to a large extent by the application of matrix-matched standards to correct for matrix-induced signal suppression, as only a few analytes such as nivalenol and the fumonisins exhibited incomplete extraction. For deoxynivalenol and zearalenone, the trueness of the method was confirmed through the analysis of certified reference materials. Copyright 2006 John Wiley & Sons, Ltd. [source]


Development of a multi-residue method for the determination of 18 carbamates in tobacco by high-performance liquid chromatography/positive electrospray ionisation tandem mass spectrometry

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 4 2006
B. Mayer-Helm
A multi-residue method for the determination of carbamates in tobacco was developed by high-performance liquid chromatography (HPLC) triple quadrupole mass spectrometry (MS). A rapid sample preparation consisted of an extraction step with methanol, centrifugation and 1:1 dilution with aqueous 10,mM ammonium acetate. After filtration these extracts were directly analysed by reversed-phase HPLC coupled to positive electrospray ionisation tandem mass spectrometry operated in the multiple reaction monitoring mode. Capillary voltage and dwell times were optimised to reduce matrix effects and to increase sensitivity. The method was validated for the determination of 18 carbamates in three main types of raw tobacco and three tobacco products. The interday accuracy ranged between 80 and 110% with a relative standard deviation (RSD) of <30%. The limits of quantification (LOQs) ranged between 0.01 and 0.04,ppm for almost all carbamates, except aldicarb sulfone, carbofuran, and pebulate, with LOQs between 0.10 and 0.20,ppm. These LOQs were clearly below the guidance residue levels defined by the Agrochemical Advisory Committee of CORESTA, an association of organisations having scientific research relative to tobacco. Copyright 2006 John Wiley & Sons, Ltd. [source]


Gaseous H5P2O8, Ions: A Theoretical and Experimental Study on the Hydrolysis and Synthesis of Diphosphate Ion

CHEMISTRY - A EUROPEAN JOURNAL, Issue 22 2004
Federico Pepi Prof.
Abstract The structure and reactivity of gaseous H5P2O8, ions obtained from the chemical ionization (CI) of an H4P2O7/H2O mixture and from electrospray ionization (ESI) of CH3CN/H2O/H4P2O7 solutions were investigated by Fourier transform ion cyclotron (FTICR) and triple quadrupole mass spectrometry. Theoretical calculations performed at the B3LYP/6-31+G* level of theory and collisionally activated dissociation (CAD) mass spectrometric results allowed the ionic population obtained in the CI conditions to be structurally characterized as a mixture of gaseous [H3P2O7,,,H2O],, [H3PO4,,,H2PO4],, and [PO3,,,H3PO4,,,H2O], clusters. The energy profile emerging from theoretical calculations affords insight into the mechanism of diphosphate ion hydrolysis and synthesis. [source]