scholarly journals Integrating automation and LC/MS for drug discovery bioanalysis

2002 ◽  
Vol 24 (1) ◽  
pp. 1-7 ◽  
Author(s):  
David T. Rossi
Keyword(s):  
Drug Discovery ◽  
Sample Preparation ◽  
Biological Fluid ◽  
Multiple Reaction Monitoring ◽  
Feasibility Studies ◽  
Integrated Approach ◽  
Sample Collection ◽  
High Concentration ◽  
Sample Handling ◽  
Flight Mass Spectrometry

A novel, integrated approach for automated sample handling in drug discovery bioanalysis is described. The process includes aspects of animal study design, biological sample collection, sample processing and high-throughput APILC/MS operating in under multiple reaction monitoring (MRM). A semi-automated 96-well liquid—liquid extraction technique for biological fluid sample preparation was developed and used in conjunction with the integrated sample-handling approach. One plate of samples could be prepared within 1.5 h compared with 4 h for a manual approach, and the resulting 96-well plate of extracts was directly compatible with the LC/MS. Feasibility studies for the development of the process included sample collection map generation and information management, sample collection formatting, evaluation of alternative dilution schemes for high-concentration samples, choice of biological fluid, and evaluating the capabilities of the two liquid-handling workstations. Numerous comparisons between the new approach and conventional sample-handling approaches gave equivalent drug-quantitation results for several example compounds. This new sampling process has approximately doubled the efficiency (as measured by studies assayed per month) of drug discovery bioanalysis in our laboratory. The approach was also used in conjunction with time-of-flight mass spectrometry instrumentation (LC/TOF/MS) to quantify and characterize the disposition of simultaneously dosed example drug compounds in the rat. Likely strategies for future automated sample preparation workstations are described.

scholarly journals Pursuing Experimental Reproducibility: An Efficient Protocol for the Preparation of Cerebrospinal Fluid Samples for NMR-Based Metabolomics and Analysis of Sample Degradation

Metabolites ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 251
Author(s):  
Benjamin Albrecht ◽  
Elena Voronina ◽  
Carola Schipke ◽  
Oliver Peters ◽  
Maria Kristina Parr ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Sample Preparation ◽  
Ph Control ◽  
Sample Storage ◽  
Sample Collection ◽  
Experimental Conditions ◽  
Sample Handling ◽  
Sample Stability ◽  
Standard Operating ◽  
New Biomarkers

NMR-based metabolomics investigations of human biofluids offer great potential to uncover new biomarkers. In contrast to protocols for sample collection and biobanking, procedures for sample preparation prior to NMR measurements are still heterogeneous, thus compromising the comparability of the resulting data. Herein, we present results of an investigation of the handling of cerebrospinal fluid (CSF) samples for NMR metabolomics research. Origins of commonly observed problems when conducting NMR experiments on this type of sample are addressed, and suitable experimental conditions in terms of sample preparation and pH control are discussed. Sample stability was assessed by monitoring the degradation of CSF samples by NMR, hereby identifying metabolite candidates, which are potentially affected by sample storage. A protocol was devised yielding consistent spectroscopic data as well as achieving overall sample stability for robust analysis. We present easy to adopt standard operating procedures with the aim to establish a shared sample handling strategy that facilitates and promotes inter-laboratory comparison, and the analysis of sample degradation provides new insights into sample stability.

Shock-tube study of the decomposition of octamethylcyclotetrasiloxane and hexamethylcyclotrisiloxane

2020 ◽  
Vol 234 (7-9) ◽  
pp. 1395-1426 ◽  
Author(s):  
Paul Sela ◽  
Sebastian Peukert ◽  
Jürgen Herzler ◽  
Christof Schulz ◽  
Mustapha Fikri
Keyword(s):  
Mass Spectrometry ◽  
Shock Tube ◽  
High Repetition Rate ◽  
Rate Coefficients ◽  
Gas Chromatography Mass Spectrometry ◽  
High Concentration ◽  
Gas Phase Chemistry ◽  
Reflected Shock ◽  
Flight Mass Spectrometry ◽  
Phase Chemistry

AbstractShock-tube experiments have been performed to investigate the thermal decomposition of octamethylcyclotetrasiloxane (D4, Si4O4C8H24) and hexamethylcyclotrisiloxane (D3, Si3O3C6H18) behind reflected shock waves by gas chromatography/mass spectrometry (GC/MS) and high-repetition-rate time-of-flight mass spectrometry (HRR-TOF-MS) in a temperature range of 1160–1600 K and a pressure range of 1.3–2.6 bar. The main observed stable products were methane (CH4), ethylene (C2H4), ethane (C2H6), acetylene (C2H2) and in the case of D4 pyrolysis, also D3 was measured as a product in high concentration. A kinetics sub-mechanism accounting for the D4 and D3 gas-phase chemistry was devised, which consists of 19 reactions and 15 Si-containing species. The D4/D3 submechanism was combined with the AramcoMech 2.0 (Li et al., Proc. Combust. Inst. 2017, 36, 403–411) to describe hydrocarbon chemistry. The unimolecular rate coefficients for D4 and D3 decomposition are represented by the Arrhenius expressions ktotal/D4(T) = 2.87 × 1013 exp(−273.2 kJ mol−1/RT) s−1 and ktotal/D3(T) = 9.19 × 1014 exp(−332.0 kJ mol−1/RT) s−1, respectively.

scholarly journals Sustainability in Construction Projects: A Systematic Literature Review

2021 ◽  
Vol 13 (4) ◽  
pp. 1932 ◽  
Author(s):  
Reza Kiani Mavi ◽  
Denise Gengatharen ◽  
Neda Kiani Mavi ◽  
Richard Hughes ◽  
Alistair Campbell ◽  
...  
Keyword(s):  
Project Management ◽  
Structural Equation ◽  
Construction Projects ◽  
Feasibility Studies ◽  
Integrated Approach ◽  
Sustainable Construction ◽  
Fuzzy Decision Making ◽  
Eigenvector Centrality ◽  
Mathematical Techniques ◽  
New Research

This paper aims to identify the major research concepts studied in the literature of sustainability in construction projects. Two bibliometric analysis tools—(a) BibExcel and (b) Gephi, were used to analyze the bibliometrics indices of papers and visualize their interrelations as a network, respectively. Therefore, a research focus parallelship network (RFPN) analysis and keyword co-occurrence network (KCON) analysis were performed to uncover the primary research themes. The RFPN analysis clustered the studies into three major categories of evaluating sustainability, project management for sustainability, and drivers of sustainable construction. The KCON analysis revealed that while each paper had a different focus, the underlying concept of all clusters was sustainability, construction, and project management. We found that while ‘sustainability’ was the leading keyword in the first cluster, i.e., evaluating sustainability, it was the second top keyword with the eigenvector centrality of over 0.94 in the other two clusters. We also found that the concept of sustainability should be included in construction projects from the early stages of design and feasibility studies and must be monitored throughout the project life. This review showed that previous researchers used a variety of statistical and mathematical techniques such as structural equation modelling and fuzzy decision-making methods to study sustainability in construction projects. Using an integrated approach to identifying the research gaps in this area, this paper provides researchers with insights on how to frame new research to study sustainability in construction projects.

Influence of Storage Conditions, Sample Handling, Sample Preparation, and Repeated Analysis on the Measured Flash Point and Hydrocarbon Composition of Jet A

Fuel ◽  
2021 ◽  
Vol 305 ◽  
pp. 121399
Author(s):  
Brent A. Modereger ◽  
Sarah E. Nowling ◽  
Wan Tang Jeff Zhang ◽  
Mackenzie L. Jones ◽  
Nathan Chapman ◽  
...  
Keyword(s):  
Sample Preparation ◽  
Hydrocarbon Composition ◽  
Storage Conditions ◽  
Flash Point ◽  
Sample Handling ◽  
Repeated Analysis

scholarly journals Qualitative analysis of 7- and 8-hydroxyzolpidem and discovery of novel zolpidem metabolites in postmortem urine using liquid chromatography–tandem mass spectrometry

2022 ◽  
Author(s):  
Koji Yamaguchi ◽  
Hajime Miyaguchi ◽  
Youkichi Ohno ◽  
Yoshimasa Kanawaku
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Pyridine Ring ◽  
Multiple Reaction Monitoring ◽  
Fragmentation Pattern ◽  
The Novel ◽  
Flight Mass Spectrometry ◽  
Urine Extract ◽  
Liquid Chromatography Tandem Mass ◽  
Characteristic Fragmentation

Abstract Purpose Zolpidem (ZOL) is a hypnotic sometimes used in drug-facilitated crimes. Understanding ZOL metabolism is important for proving ZOL intake. In this study, we synthesized standards of hydroxyzolpidems with a hydroxy group attached to the pyridine ring and analyzed them to prove their presence in postmortem urine. We also searched for novel ZOL metabolites in the urine sample using liquid chromatography–triple quadrupole mass spectrometry (LC-QqQMS) and liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QqTOFMS). Methods 7- and 8-Hydroxyzolpidem (7OHZ and 8OHZ, respectively) were synthesized and analyzed using LC-QqQMS. Retention times were compared between the synthetic standards and extracts of postmortem urine. To search for novel ZOL metabolites, first, the urine extract was analyzed with data-dependent acquisition, and the peaks showing the characteristic fragmentation pattern of ZOL were selected. Second, product ion spectra of these peaks at various collision energies were acquired and fragments that could be used for multiple reaction monitoring (MRM) were chosen. Finally, MRM parameters were optimized using the urine extract. These peaks were also analyzed using LC-QqTOFMS. Results The presence of 7OHZ and 8OHZ in urine was confirmed. The highest peak among hydroxyzolpidems was assigned to 7OHZ. The novel metabolites found were zolpidem dihydrodiol and its glucuronides, cysteine adducts of ZOL and dihydro(hydroxy)zolpidem, and glucuronides of hydroxyzolpidems. Conclusions The presence of novel metabolites revealed new metabolic pathways, which involve formation of an epoxide on the pyridine ring as an intermediate.

MALDI-TOF MS and its requirements for fungal identification.

2021 ◽  
pp. 119-140
Author(s):  
Cledir Santos ◽  
Paula Galeano ◽  
Reginaldo Lima Neto ◽  
Manoel Marques Evangelista Oliveira ◽  
Nelson Lima
Keyword(s):  
Sample Preparation ◽  
Black Box ◽  
Data Sets ◽  
Maldi Tof Ms ◽  
Maldi Tof ◽  
Flight Mass Spectrometry ◽  
Fungal Identification ◽  
Identification Of Fungi ◽  
Tof Ms

Abstract Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) is now used as a routine technique for the fast and reliable identification of fungi at the species level and, currently, it represents an important phenotypic methodology based on proteomic profiles. The main limitations to MALDI-TOF MS for fungal identification are related to sample quality (e.g. quality of biological material such as rigidity or pigmentation of cell walls), sample preparation (e.g. the myriad of sample preparation methodologies that deliver different data sets to different MALDI-TOF MS databases) and the databases themselves (e.g. the 'black-box' commercial databases). This chapter presents an overview and discussion of the use of MALDI-TOF MS for fungal identification. The major known limitations of the technique for fungal taxonomy, and how to overcome these, are also discussed.

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