Modern MALDI time‐of‐flight mass spectrometry

This paper focuses on development of time‐of‐flight (TOF) mass spectrometry in response to the invention of matrix‐assisted laser desorption/ionization (MALDI). Before this breakthrough ionization technique for nonvolatile molecules, TOF was generally considered as a useful tool for exotic studies of ion properties but was not widely applied to analytical problems. Improved TOF instruments and software that allow the full potential power of MALDI to be applied to difficult biological applications are described. A theoretical approach to the design and optimization of MALDI‐TOF instruments for particular applications is presented. Experimental data are provided that are in excellent agreement with theoretical predictions of resolving power and mass accuracy. Data on sensitivity and dynamic range using kilohertz laser rates are also summarized. These results indicate that combinations of high‐performance MALDI‐TOF and TOF‐TOF with off‐line high‐capacity separations may ultimately provide throughput and dynamic range several orders of magnitude greater than those currently available with electrospray LC‐MS and MS‐MS. Copyright © 2009 John Wiley & Sons, Ltd.     

Rapid screening and determination of 4‐chloroamphetamine in saliva by paper spray‐mass spectrometry and capillary electrophoresis‐mass spectrometry

A novel drug‐screening system, consisting of paper spray‐MS (PS‐MS) and a CE‐ESI‐MS method was developed. This system can be easily switched either to PS‐MS for rapidly screening samples or to the traditional CE‐ESI‐MS method for separation and to obtain detailed mass spectral information, while sharing the same mass spectrometer. In the former case, when a sharp (15°‐tip) chromatography paper was used, the optimized distance from the paper tip to the mass inlet was 7.7 mm, whereas the optimized distance for the CE‐ESI tip was ～13.5 mm. Using 4‐chloroamphetamine as a model compound, the LODs for PS‐MS and CE‐ESI‐MS were determined to ～0.1 and 0.25 ppm, respectively. Comparisons of results obtained using PS‐MS and CE‐ESI‐MS and the experimental conditions are described.     

Gas‐phase fragmentation reactions of protonated benzofuran‐ and dihydrobenzofuran‐type neolignans investigated by accurate‐mass electrospray ionization tandem mass spectrometry

We have investigated gas‐phase fragmentation reactions of protonated benzofuran neolignans (BNs) and dihydrobenzofuran neolignans (DBNs) by accurate‐mass electrospray ionization tandem and multiple‐stage (MSⁿ) mass spectrometry combined with thermochemical data estimated by Computational Chemistry. Most of the protonated compounds fragment into product ions B ([M + H–MeOH]⁺), C ([ B –MeOH]⁺), D ([ C –CO]⁺), and E ([ D –CO]⁺) upon collision‐induced dissociation (CID). However, we identified a series of diagnostic ions and associated them with specific structural features. In the case of compounds displaying an acetoxy group at C‐4, product ion C produces diagnostic ions K ([ C –C₂H₂O]⁺), L ([ K –CO]⁺), and P ([ L –CO]⁺). Formation of product ions H ([ D –H₂O]⁺) and M ([ H –CO]⁺) is associated with the hydroxyl group at C‐3 and C‐3′, whereas product ions N ([ D –MeOH]⁺) and O ([ N –MeOH]⁺) indicate a methoxyl group at the same positions. Finally, product ions F ([ A –C₂H₂O]⁺), Q ([ A –C₃H₆O₂]⁺), I ([ A –C₆H₆O]⁺), and J ([ I –MeOH]⁺) for DBNs and product ion G ([ B –C₂H₂O]⁺) for BNs diagnose a saturated bond between C‐7′ and C‐8′. We used these structure‐fragmentation relationships in combination with deuterium exchange experiments, MSⁿ data, and Computational Chemistry to elucidate the gas‐phase fragmentation pathways of these compounds. These results could help to elucidate DBN and BN metabolites in in vivo and in vitro studies on the basis of electrospray ionization ESI‐CID‐MS/MS data only.     

Quadrupole‐time‐of‐flight mass spectrometry screening for synthetic cannabinoids in herbal blends

‘Legal highs’ are novel substances which are intended to elicit a psychoactive response. They are sold from ‘head shops’, the internet and from street suppliers and may be possessed without legal restriction. Several months ago, a 19‐year‐old woman came searching for medical treatment as she had health problems caused by smoking legal highs. The substances were sold as herbal blends in plastic bags under four different labels. In this work, samples of these herbal blends have been analysed to investigate the presence of psychoactive substances without any reference standard being available at the laboratory. A screening strategy for a large number of synthetic and natural cannabinoids has been applied based on the use of ultra‐high pressure liquid chromatography coupled to quadrupole‐time of flight mass spectrometry (UHPLC‐QTOF MS) under MS^E mode. A customized home‐made database containing literature‐based exact masses for parent and product ions of around 200 synthetic and natural cannabinoids was compiled. The presence of the (de)protonated molecule measured at its accurate mass was evaluated in the samples. When a peak was detected, collision‐induced dissociation fragments and characteristic isotopic ions were also evaluated and used for tentative identification. After this tentative identification, four synthetic cannabinoids (JWH‐081, JWH‐250, JWH‐203 and JWH‐019) were unequivocally confirmed by subsequent acquisition of reference standards. The presence in the herbal blends of these synthetic cannabinoids might explain the psychotic and catatonic symptoms observed in the patient, as JWH compounds could act as potent agonists of CB₁ and CB₂ receptors located in the Limbic System and Basal ganglia of the human brain. Copyright © 2013 John Wiley & Sons, Ltd.     

A small high‐irradiance laser ionization time‐of‐flight mass spectrometer

A small high‐irradiance laser ionization time‐of‐flight mass spectrometer (LI‐TOFMS) with orthogonal sample introduction was described. High irradiance of 6 × 10¹⁰ W/cm² at 532 nm from a Nd : YAG laser was applied in the experiment to get a high ionization degree in plasma and to dissociate the interferential polyatomic ions. Meanwhile, the interferential multiply charged ions resulted by high‐irradiance were nearly eliminated in the spectrum by utilizing helium as the buffer gas in the ion source due to three‐body recombination, which resulted in a relatively clean background. Improved signal stability was obtained by automated step moving of the sample stage in short time intervals. By using two sets of Einzel lens in transport system, nearly uniform relative sensitivity coefficients (RSCs) were achieved for most of metal elements including light ions which were detected in extremely low sensitivity in previous hexapole transportation instrument. The resolving power reaches 2200, and the detection limits (DLs) are 10^?6 g/g for metal elements in the steel standard. Copyright © 2009 John Wiley & Sons, Ltd.     

Glycerophospholipid profiling by high‐performance liquid chromatography/mass spectrometry using exact mass measurements and multi‐stage mass spectrometric fragmentation experiments in parallel

A profiling method for glycerophospholipids (GPs) in biological samples was developed using reversed‐phase high‐performance liquid chromatography (RP‐HPLC) coupled to hybrid linear ion trap‐Fourier transform ion cyclotron resonance mass spectrometry (LIT‐FTICRMS) with electrospray ionization (ESI) in the negative ionization mode. The method allowed qualitative (identification and structure elucidation) and relative quantitative determination of various classes of GPs including phosphatidylcholines, phosphatidylethanolamines, phosphatidylinositols, phosphatidylserines, phosphatidic acids, phosphatidylglycerols, and cardiolipins in a single experiment. Chromatographic separation was optimized by the examination of different buffer systems and special emphasis was paid on the detection by ESI‐MS. The hybrid LIT‐FTICRMS system was operated in the data‐dependent mode, switching automatically between FTICRMS survey scans and LIT‐MS/MS experiments. Thereby, exact masses for elemental composition determination and fragmentation data for identification and assignment of fatty acid residues are provided at the same time. The low absolute instrumental limits of detection (0.05 pmol for phosphatidylglycerol to 1 pmol for phosphatidic acid) complemented by a linear dynamic range of 1.5 to 2.5 orders of magnitude facilitated the relative quantification of GP species in a lipid extract from Saccharomyces cerevisiae. The developed method is a valuable tool for in‐depth GP profiling of biological systems. Copyright © 2009 John Wiley & Sons, Ltd.