bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitation of midazolam in human plasma by automated chip‐based infusion nanoelectrospray tandem mass spectrometry
Authors: Kapron James T. , Pace Ellen , Van Pelt Colleen K. , Henion Jack 
Published: September 2003

AbstractAn automated chip‐based infusion nanoelectrospray ionization (nanoESI) platform was used to demonstrate reproducible quantitation of drug molecules from biological matrices. Three sample preparation strategies were explored including protein precipitation of plasma with acetonitrile, de‐salting of the plasma, and a combination of protein precipitation with subsequent de‐salting of the dried and reconstituted extract. The best results were obtained when fortified human plasma samples containing midazolam were precipitated with acetonitrile containing alprazolam as the internal standard (IS). The supernatant was concentrated to dryness, reconstituted in aqueous acid, and de‐salted by automated reversed‐phase solid‐phase extraction (SPE) prior to infusion nanoESI‐MS/MS. Analyses employed a triple quadrupole mass spectrometer operated in selected reaction monitoring (SRM) mode. Each sample was infused for approximately 10 s and the resulting ion current profiles were integrated. Area ratios were used for regression analysis of standard samples (1.5–500 ng/mL). Quality control samples (3, 250, and 400 ng/mL) in five replicates from three different analysis days demonstrated intra‐assay precision (≤16%), inter‐assay precision (≤5%), and overall accuracy (±9% deviation). Infusion reproducibility of the assay was established by analyzing extracts after storage for 24 h at ambient temperature. Control plasma samples from six different sources probed the potential utility of this technique for the analysis of clinical samples. At the lower limit of quantitation (LLQ), variability and mean overall accuracy were ≤13% CV and ±3% deviation, respectively, while at the upper limit of quantitation (ULQ) variability and mean overall accuracy were ≤9% CV and ±9% deviation, respectively. Inter‐chip variability was established by determining standard sample extracts across five different chips (≤12% CV). Throughput for the assay was 55 s per sample, although this time may be shortened to 40 s per sample with recent improvements in the automated nanoESI system. No contamination or carryover was observed using this promising automated nanoESI‐MS/MS platform. Copyright © 2003 John Wiley & Sons, Ltd.
Parallel preparative high‐performance liquid chromatography with on‐line molecular mass characterization
Authors: Edwards Christine , Liu Jianbo , Smith Thomas J. , Brooke Daniel , Hunter David J. , Organ Andrew , Coffey Patrick 
Published: September 2003

AbstractHigh‐throughput chemistry (HTC) is now an integral part of the lead discovery process in many pharmaceutical and related chemical companies. As this process becomes refined or improved, with the integration of systems with enhanced capabilities, and the requirement for quality compounds of high purity increases, purification is often considered a bottleneck. Although a wide range of purification techniques is available, high‐performance liquid chromatography (HPLC) is usually the preferred method of purification to produce high‐purity compounds. Parallel preparative HPLC with robust UV‐guided fraction collection has been shown to reduce the bottleneck and complement the parallel synthesis systems. However, despite the success of this technique, post‐purification analysis of fractions to identify the target compound adds an additional level of complexity. This paper describes the interfacing of the Biotage Parallex™ with the MUX™ interface on a single quadrupole mass spectrometer, thus combining robust UV‐guided fractionation with on‐line MS characterization. Copyright © 2003 John Wiley & Sons, Ltd.
Electrospray ionization mass spectrometry in studies of aluminium(III)–ligand solution equilibria
Authors: Di Marco Valerio B. , Bombi G. Giorgio , Tubaro Michela , Traldi Pietro 
Published: September 2003

AbstractElectrospray ionization mass spectrometry (ESI‐MS) has been applied to the study of solution equilibria between Al(III) and the two ligands 4‐hydroxy‐3‐pyridinecarboxylic acid (4H3P) and 3‐hydroxy‐4‐pyridinecarboxylic acid (3H4P). The results compare well with the speciation data obtained from potentiometric, UV‐visible spectroscopy, and NMR measurements. This agreement suggests the applicability of ES‐MS to the study of more complicated aluminium–ligand systems. Copyright © 2003 John Wiley & Sons, Ltd.
Analysis of Colubroidea snake venoms by liquid chromatography with mass spectrometry: evolutionary and toxinological implications
Authors: Fry Bryan G. , Wüster Wolfgang , Ryan Ramjan Sheik Fadil , Jackson Timothy , Martelli Paolo , Kini R. Manjunatha 
Published: September 2003

AbstractThe evolution of the venomous function of snakes and the diversification of the toxins has been of tremendous research interest and considerable debate. It has become recently evident that the evolution of the toxins in the advanced snakes (Colubroidea) predated the evolution of the advanced, front‐fanged delivery mechanisms. Historically, the venoms of snakes lacking front‐fanged venom‐delivery systems (conventionally grouped into the paraphyletic family Colubridae) have been largely neglected. In this study we used liquid chromatography with mass spectrometry (LC/MS) to analyze a large number of venoms from a wide array of species representing the major advanced snake clades Atractaspididae, Colubrinae, Elapidae, Homalopsinae, Natricinae, Psammophiinae, Pseudoxyrhophiinae, Xenodontinae, and Viperidae. We also present the first sequences of toxins from Azemiops feae as well as additional toxin sequences from the Colubrinae. The large body of data on molecular masses and retention times thus assembled demonstrates a hitherto unsuspected diversity of toxins in all lineages, having implications ranging from clinical management of envenomings to venom evolution to the use of isolated toxins as leads for drug design and development. Although definitive assignment of a toxin to a protein family can only be done through demonstrated structural studies such as N‐terminal sequencing, the molecular mass data complemented by LC retention information, presented here, do permit formulation of reasonable hypotheses concerning snake venom evolution and potential clinical effects to a degree not possible till now, and some hypotheses of this kind are proposed here. The data will also be useful in biodiscovery. Copyright © 2003 John Wiley & Sons, Ltd.
Direct detection of particles formed by laser ablation of matrices during matrix‐assisted laser desorption/ionization
Authors: Alves Sandra , Kalberer Markus , Zenobi Renato 
Published: September 2003

AbstractWe report the detection of nanoparticles formed by irradiating matrix‐assisted laser desorption/ionization (MALDI) matrix samples. This is direct evidence for the ejection of large size aggregates in the MALDI process. Nanometer‐size particles were generated via a tunable solid‐state UV laser, irradiating a sample placed in a nitrogen atmosphere. Size distribution measurements were performed using a differential mobility analyzer and a condensation particle counter. Particles in the 10–1000 nm size range were detected. The dependence of the particle size distribution on the laser fluence, wavelength and matrix was investigated. The observed effects are discussed and related to the MALDI ablation dynamics and gas‐phase processes. Copyright © 2003 John Wiley & Sons, Ltd.
A microcapillary trap cartridge‐microcapillary high‐performance liquid chromatography electrospray ionization emitter device capable of peptide tandem mass spectrometry at the attomole level on an ion trap mass spectrometer with automated routine operation
Authors: Yi Eugene C. , Lee Hookeun , Aebersold Ruedi , Goodlett David R. 
Published: September 2003

AbstractReversed‐phase microcapillary chromatography (RP‐μLC) combined with electrospray ionization tandem mass spectrometry (ESI‐MS/MS) is one of two prevailing techniques in proteomic analysis, the other being matrix‐assisted laser desorption/ionization (MALDI). Despite the arguably better dynamic range obtainable with ESI, MALDI is increasingly popular due to ease of use, ruggedness and the ability to decouple separation from ionization. By contrast, in order to take advantage of the sensitivity and dynamic range afforded by the concentration‐dependent nature of ESI, it is directly coupled to separations that take place in small i.d. RP‐μLC columns. This gain in sensitivity often comes at a loss of ruggedness due to clogging of the small i.d. RP‐μLC columns, one result of which is limited sample throughput. Here we describe a combined μpre‐column‐μLC‐ESI device that is sensitive, rugged and modular in design allowing facile construction and troubleshooting. Due to low signal‐to‐noise as little as 1 attomole of a peptide can be selected by data‐dependent methods for collision‐induced dissociation. Importantly, the resulting tandem mass spectrum is of high enough quality to identify the peptide sequence by a database search against a complex database using SEQUEST. Finally, the device is demonstrated to be rugged as judged by >60 consecutive reversed‐phase μLC separations on complex peptide mixtures before chromatographic resolution is degraded. Copyright © 2003 John Wiley & Sons, Ltd.
Simultaneous quantitative analysis of three drugs by high‐performance liquid chromatography/electrospray ionization mass spectrometry and its application to cassette in vitro metabolic stability studies
Authors: Rajanikanth M. , Madhusudanan K. P. , Gupta R. C. 
Published: September 2003

AbstractA sensitive and selective liquid chromatography/electrospray mass spectrometry (LC/ESI‐MS) method has been developed for the simultaneous quantitative determination of three new chemical entities (NCEs), of the class of aryloxy‐substituted aryl piperazines, in rat liver S9 fraction. S9 fraction samples (0.1 mL) were simply extracted with 2% isopropanol in diethyl ether and the extracts analyzed by HPLC with the detection of the analytes in the selective ion recording (SIR) mode. The determination of the analytes was accurate and reproducible, with a limit of quantification of 50 ng/mL for all the analytes in rat liver S9 fraction. The standard calibration curve for the analytes was linear over the concentration range 50–4000 ng/mL. Analysis accuracy and precision over the concentration range were lower than ±15%. This method offered significant increase in the analytical throughput, which is illustrated by the ‘N‐in‐One’ study of metabolic stability of the compounds in rat liver S9 fractions. The quantitative results from the ‘N‐in‐One’ procedure correlated well with those obtained from conventional discrete analyses. In addition, the samples were reanalyzed to allow for detection of the metabolites formed during the same incubation. The metabolites were first characterized by nominal mass measurement of the corresponding protonated molecules. Subsequent tandem mass spectrometry allowed confirmation of the detected metabolites. Copyright © 2003 John Wiley & Sons, Ltd.
Trace determination of organotin compounds in water, sediment and mussel samples by low‐pressure gas chromatography coupled to tandem mass spectrometry
Authors: Vidal J. L. Martínez , Vega A. Belmonte , Arrebola F. J. , González‐Rodríguez M. J. , Sánchez M. C. Morales , Frenich A. Garrido 
Published: September 2003

AbstractA fast method for the determination of eight organotin compounds (OTs), monobutyltin (MBT), dibutyltin (DBT), tributyltin (TBT), tetrabutyltin (TeBT), monophenyltin (MPhT), diphenyltin (DPhT), triphenyltin (TPhT) and tetraphenyltin (TePhT), in water, sediments and mussels, was developed using low‐pressure gas chromatography/tandem mass spectrometry (LPGC/MS/MS). The method is based on sodium diethyldithiocarbamate (DDTC) complexation of the ionic organotins, followed by extraction of the target matrices and derivatization by a Grignard reagent, as described in a previously published method for water samples (S. Tsunoi et al., J. Chromatogr. A 2002; 962: 197). Solid‐phase extraction was selected as extraction method from water samples after comparison with liquid–liquid extraction, but extraction of the OTs from sediment and mussel samples was performed using toluene. Matrix‐matched calibration standards were used to minimize matrix effects. The analytical process was validated by the analysis of spiked blank samples. Performance characteristics such as linearity, detection limit (LOD), quantitation limit (LOQ), precision, and recovery were determined. Recoveries of OTs in spiked matrices ranged from 86–108% in water and from 78–110% in sediments and mussels, with precision values lower than 18%. Detection limits ranged from 0.1–9.6 ng L−1 in water, and 0.03–6.10 μg kg−1 in the other matrices. The present implementation of LPGC rather than conventional capillary GC permitted use of large‐volume injection and reduced analysis time by a factor of two. The proposed methodology was applied to the determination of OTs in real samples of water, marine sediments and mussels from the west coast of the Mediterranean Sea (Spain). Copyright © 2003 John Wiley & Sons, Ltd.
Investigation by solid‐phase microextraction and gas chromatography/mass spectrometry of trail pheromones in ants
Authors: Tullio Alessandra Di , Angelis Francesco De , Reale Samantha , Grasso Donato A. , Visicchio Roberto , Castracani Cristina , Mori Alessandra , Moli Francesco Le 
Published: September 2003

AbstractThe Dufour's gland content of workers of two ant species of the genus Messor has been analyzed by solid‐phase microextraction and gas chromatography with mass spectrometry (GC/MS). The structures of the compounds in the pheromonal mixtures have been determined. In both cases only one intact gland, inserted in a properly dimensioned capillary vial, is sufficient to produce a clean and fully interpretable GC/MS profile. It is worth noting that, for the first time in Messor ants, farnesol has been detected as a minor component of glandular secretion in Messor capitatus. Copyright © 2003 John Wiley & Sons, Ltd.
Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry of phosphorylated compounds using a novel phosphate capture molecule
Authors: Takeda Hironori , Kawasaki Akihiko , Takahashi Makoto , Yamada Atsushi , Koike Tohru 
Published: September 2003

AbstractThis paper introduces a simple, rapid, and sensitive procedure for the analysis of phosphorylated compounds (ROPO32−) by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS). The method is based on a characteristic mass shift and a total‐charge change (from −2 to +1) of the phosphate residue due to complexation of ROPO32− with a dinuclear zinc(II) complex (1,3‐bis[bis(2‐pyridinylmethyl)amino]‐2‐propanolato dizinc(II) complex, Zn2L3+) in aqueous solution at physiological pH. Furthermore, the use of single zinc‐isotope derivatives (64Zn2L3+ and 68Zn2L3+) enables improvement of the sensitivity and accuracy of the analysis. Copyright © 2003 John Wiley & Sons, Ltd.
Quantitative analysis of betulinic acid in mouse, rat and dog plasma using electrospray liquid chromatography/mass spectrometry
Authors: Cheng Xun , Shin Young Geun , Levine Barry S. , Smith Adaline C. , Tomaszewski Joseph E. , van Breemen Richard B. 
Published: September 2003

AbstractBetulinic acid is under development as a therapeutic agent for the treatment of metastatic malignant melanoma. In support of pharmacokinetic and toxicological evaluations, a robust assay based on liquid chromatography/mass spectrometry (LC/MS) was developed for the quantitative analysis of betulinic acid. Sample preparation consisted of deproteinization of the plasma by the addition of three volumes of acetonitrile and one volume of methanol followed by centrifugation. Aliquots of the supernatant were analyzed using an isocratic reversed‐phase high‐performance liquid chromatography (HPLC) system coupled to a negative ion electrospray mass spectrometer. Deprotonated molecules of betulinic acid and the isomeric internal standard oleanolic acid were detected using selected ion monitoring at m/z 455. The limit of detection of betulinic acid was 0.5 pg (1.1 fmol) injected on‐column (50 pg/mL, 10 μL injection volume), and the limit of quantitation was 2 pg (4.4 fmol, 200 pg/mL, 10 μL injection volume). Betulinic acid was stable in plasma samples at −20°C for at least 3 weeks. The intra‐day and inter‐day coefficients of variation of the assay were ≤6.4 and ≤9.0%, respectively. The utility of the assay was demonstrated by analyzing betulinic acid spiked into mouse, rat and dog plasma, by determining the extent of binding of betulinic acid to plasma proteins, and by measuring betulinic acid in mouse and rat plasma following intraperitoneal or intravenous administration in vivo. At 15 and 25 μg/mL in mouse, rat or dog plasma, betulinic acid was 99.99% bound to serum proteins, and, at 5 μg/mL, betulinic acid was ≥99.97% bound. Copyright © 2003 John Wiley & Sons, Ltd.
Validation of a screening method for corticosteroids in doping analysis by liquid chromatography/tandem mass spectrometry
Authors: Deventer K. , Delbeke F. T. 
Published: September 2003

AbstractA selective and sensitive method for the screening of nine corticosteroids in human urine has been validated. Analyses were performed using an ion trap instrument equipped with an electrospray ionisation (ESI) interface. All corticosteroids were separated in less than 20 min after liquid/liquid extraction with diethyl ether. The limit of detection for all substances was 4 ng/mL or lower. The method was applied to detect betamethasone after the intramuscular injection of Diprophos®. Betamethasone could be detected for up to 12 days after administration. Validation of the chromatographic separation and mass spectrometric identification of mixtures of betamethasone and dexamethasone are also presented. Copyright © 2003 John Wiley & Sons, Ltd.
Differentiation of isomeric polyaromatic hydrocarbons by electrospray Ag(I) cationization mass spectrometry
Authors: Ming Ng Kwan , Ling Ma Ngai , Wai Tsang Chun 
Published: September 2003

AbstractAbundant Ag(I)‐cationized complexes of 13 polyaromatic hydrocarbons (PAHs), [Ag+PAH]+ and [Ag+2(PAH)]+, were readily generated by electrospray ionization (ESI). In‐source collision‐induced dissociation (CID) of the [Ag+2(PAH)]+ complex yielded the monomer complex [Ag+PAH]+, which fragmented further to yield the radical molecular ion [PAH]+.. Based on significant differences in relative intensities of [Ag+2(PAH)]+, [Ag+PAH]+ and [PAH]+., isomeric PAHs can be differentiated. The [PAH]+./[Ag+PAH]+ ion intensity ratio was found to increase with decreasing ionization potentials (IPs) of PAHs. The ratio was significantly different for the isomeric PAHs studied over a wide range of PAH concentrations (1.6–100 nmol/mL), and showed good measurement reproducibility; the coefficient of variation of inter‐day measurements was in the range 3–12% for four representative PAHs (n = 5). Detection limits for phenanthrene, pyrene, chrysene and benzo[a]pyrene, in the form of the monomer complexes [107Ag+PAH]+ and measured in the selected‐ion monitoring (SIM) mode, were 0.31, 0.63, 0.16 and 1.25 pmol/5 μL injection, respectively (S/N ratio ∼2–3). Copyright © 2003 John Wiley & Sons, Ltd.
Secondary ion formation of low molecular weight organic dyes in time‐of‐flight static secondary ion mass spectrometry
Authors: Lenaerts Jens , Van Vaeck Luc , Gijbels Renaat 
Published: September 2003

AbstractTime‐of‐flight static secondary ion mass spectrometry (TOF‐S‐SIMS) was used to characterize thin layers of oxy‐ and thiocarbocyanine dyes on Ag and Si. Apart from adduct ions a variety of structural fragment ions were detected for which a fragmentation pattern is proposed. Peak assignments were confirmed by comparing spectra of dyes with very similar structures. All secondary ions were assigned with a mass accuracy better than 50 ppm. The intensity of molecular ions as well as fragment ions has been studied as a function of the type of organic dye, the substrate, the layer thickness and the type of primary ion. A large yield difference of two orders of magnitude was observed between the precursor ions of cationic carbocyanine dyes and the protonated molecules of the anionic dyes. Fragment ions, on the other hand, yielded similar intensities for both types of dye. As the dye layers deposited on an Ag substrate yielded higher secondary ion intensities than those deposited on a Si substrate, the Ag metal clearly acts as a promoting agent for secondary ion formation. The effect was more pronounced for precursor signals than for fragment ions. The promoting effect decreased as the deposited layer thickness of the organic dye layer was increased. Copyright © 2003 John Wiley & Sons, Ltd.
Analysis of aromatic amines in cigarette smoke
Authors: Stabbert Regina , Schäfer Karl‐Heinz , Biefel Christine , Rustemeier Klaus 
Published: September 2003

AbstractA method for the analysis of o‐toluidine, o‐anisidine, 2‐naphthylamine, and 4‐aminobiphenyl in cigarette mainstream smoke has been developed, which combines the sensitivity of their pentafluoropropionyl (PFP) derivatives in negative ion chemical ionization (NICI) mode with the selectivity of the gas chromatography/tandem mass spectrometry (GC/MS/MS) technique. The use of four deuterated analogues as internal standards along with the application of the standard addition method results in accurate and precise results; the interday precision for the aromatic amines was 3–10% and the accuracy ranged from 97–100%. This method was applied to two American‐blend University of Kentucky reference cigarettes, eight American‐blend market cigarettes, a bright (flue‐cured) tobacco cigarette, and an electrically heated cigarette smoking system (EHCSS). For the American‐blend cigarettes there was a linear correlation between aromatic amine yields and mainstream smoke ‘tar’ (‘tar’ = total particulate matter − (nicotine + water)), whereas the bright tobacco cigarette and the EHCSS demonstrated significantly lower aromatic amine yields on an equal ‘tar’ basis. The results support the hypothesis that the nitrogen content of the tobacco, and above all the cigarette combustion temperature, are determining factors for the yields of aromatic amines in smoke. Copyright © 2003 John Wiley & Sons, Ltd.