A5002921341- Metabolomics and Mass Spectrometry Studies
- Analytical Chemistry and Chromatography
- Pharmacogenetics and Drug Metabolism
- Mass Spectrometry Techniques and Applications
- Forensic Toxicology and Drug Analysis
- Alcohol Consumption and Health Effects
- Drug Transport and Resistance Mechanisms
- Cannabis and Cannabinoid Research
- Drug-Induced Hepatotoxicity and Protection
- Computational Drug Discovery Methods
- Sulfur Compounds in Biology
- Advanced Proteomics Techniques and Applications
- Pharmacological Effects and Toxicity Studies
- Protein purification and stability
- Inflammatory mediators and NSAID effects
- Biosimilars and Bioanalytical Methods
- Peroxisome Proliferator-Activated Receptors
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Analytical Methods in Pharmaceuticals
- Biochemical effects in animals
- Traditional Chinese Medicine Analysis
- Metabolism and Genetic Disorders
- Colorectal Cancer Treatments and Studies
- Diet and metabolism studies
Soligenix (United States)
2024
Chinese Academy of Sciences
2023
China National Pharmaceutical Group Corporation (China)
2023
University of Chinese Academy of Sciences
2023
Shanghai Institute of Materia Medica
2023
Xiamen University
2019-2022
Bristol-Myers Squibb (United States)
2011-2020
Nankai University
2018
Tianjin University
2018
University of Wisconsin–Madison
2018
Lianhuaqingwen (LHQW) capsule, a herb medicine product, has been clinically proved to be effective in coronavirus disease 2019 (COVID-19) pneumonia treatment. However, human exposure LHQW components and their pharmacological effects remain largely unknown. Hence, this study aimed determine anti-COVID-19 activities. Analysis of component profiles plasma urine after repeated therapeutic dosing was conducted using combination HRMS an untargeted data-mining approach, leading detection 132...
An improved mass defect filter (MDF) method employing both drug and core structure templates was applied to the processing of high resolution liquid chromatography/mass spectrometry (LC/MS) data for detection structural characterization oxidative metabolites with defects similar or significantly different from those parent drugs. The effectiveness this approach investigated using nefazodone as a model compound, which is known undergo multiple common uncommon reactions. Through selective...
Amlodipine is a commonly prescribed calcium channel blocker for the treatment of hypertension and ischemic heart disease. The drug slowly cleared in humans primarily via dehydrogenation its dihydropyridine moiety to pyridine derivative (M9). Results from clinical drug-drug interaction studies suggest that CYP3A4/5 mediate metabolism amlodipine. However, attempts identify role CYP3A5 amlodipine based on pharmacokinetic differences between expressers nonexpressers failed. Objectives this study...
The present study was designed to apply the mass defect filter (MDF) approach screening and identification of reactive metabolites using high-resolution spectrometry. Glutathione (GSH)-trapped acetaminophen, diclofenac, carbamazepine, clozapine, p-cresol, 4-ethylphenol, 3-methylindole in human liver microsomes (HLM) were analyzed by HPLC coupled with Orbitrap or Fourier transform ion cyclotron resonance Through selective removal all ions that fall outside GSH adduct MDF template windows,...
A new strategy using a hybrid linear ion trap/Orbitrap mass spectrometer and multiple post-acquisition data mining techniques was evaluated applied to the detection characterization of in vitro metabolites indinavir. Accurate-mass, full-scan MS MS/MS sets were acquired with generic data-dependent method processed extracted-ion chromatography (EIC), mass-defect filter (MDF), product-ion (PIF), neutral-loss (NLF) techniques. The high-resolution EIC process shown be highly effective common...
The present study describes a new analytical approach for the detection and characterization of GSH-trapped reactive metabolites using multiple reaction monitoring (MRM) as survey scan to trigger acquisition enhanced product ion (EPI) spectra on triple quadrupole linear mass spectrometer. MRM step was carried out following up 114 transitions from protonated molecules potential GSH adducts their ions derived neutral loss 129 or 307 Da. transition protocols were constructed basis common...
A highly sensitive and efficient method has been developed for detection characterization of glutathione (gamma-glutamyl-cysteinylglycine, GSH)-trapped reactive metabolites using a negative precursor ion (PI) as the survey scan to trigger acquisition positive enhanced product (EPI) spectra on triple quadrupole linear trap mass spectrometer. The step was carried out monitoring anion at m/z 272, corresponding deprotonated gamma-glutamyl-dehydroalanyl-glycine originating from glutathionyl...
Reactive metabolite formation has been associated with drug-induced liver, skin, and hematopoietic toxicity of many drugs that resulted in serious clinical toxicity, leading to development failure, black box warnings, or, some cases, withdrawal from the market. In vitro vivo screening for reactive proposed widely adopted pharmaceutical industry aim minimizing property thus risk (DIT). One most common methods is thiol trapping metabolites. Although it well-documented hepatotoxins form...
Since the mid-2000s synthetic cannabinoids have been abused as recreational drugs, prompting scheduling of these substances in many countries. To circumvent legislation, manufacturers constantly market new compounds; [1-(5-fluoropentyl)indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone (XLR-11), fluorinated UR-144 analog, is one most recent and widely its use now linked with acute kidney injury. Our goal was to investigate XLR-11 metabolism for identification major urinary targets...
Recent examples have demonstrated that the high-resolution liquid chromatography/mass spectrometry (LC/MS)-based mass defect filtering (MDF) technique was effective in selectively detecting drug metabolites regardless of their molecular weights or fragmentation patterns. The main objective current study to evaluate general applicability MDF for metabolite detection typical biological matrices. Mass profiles commonly used matrices including plasma, urine, bile, and feces were obtained using...
Abstract A novel LC/MS/MS method that uses multiple ion monitoring (MIM) as a survey scan to trigger the acquisition of enhanced product ions (EPI) on hybrid quadrupole‐linear trap mass spectrometer (Q TRAP) was developed for drug metabolite identification. In MIM experiment, predicted were monitored in both Q1 and Q3. The collision energy Q2 set low value minimize fragmentation. Results from analyzing ritonavir metabolites rat hepatocytes demonstrate MIM‐EPI capable targeting larger number...
Abstract Interferences from biological matrices remain a major challenge to the in vivo detection of drug metabolites. For last few decades, predicted metabolite masses and fragmentation patterns have been employed aid metabolites liquid chromatography/mass spectrometry (LC/MS) data. Here we report application an accurate mass‐based background‐subtraction approach for comprehensive formed using troglitazone as example. A novel algorithm was applied check all ions spectra control scans within...
Currently, mass spectrometry-based protein bioanalysis is primarily achieved through monitoring the representative peptide(s) resulting from analyte digestion. However, this approach often incapable of differentiating measurement its post-translational modifications (PTMs) and/or potential biotransformation (BTX) products. This disadvantage can be overcome by direct intact analytes. Selected reaction (SRM) on triple quadrupole spectrometers has been used for protein. fragmentation efficiency...
This study was carried out to determine the metabolic pathways of buspirone and cytochrome P450 (P450) isoform(s) responsible for metabolism in human liver microsomes (HLMs). Buspirone mainly underwent <i>N</i>-dealkylation 1-pyrimidinylpiperazine (1-PP), <i>N</i>-oxidation on piperazine ring <i>N</i>-oxide (Bu <i>N</i>-oxide), hydroxylation 3′-hydroxybuspirone (3′-OH-Bu), 5-hydroxybuspirone (5-OH-Bu), 6′-hydroxybuspirone (6′-OH-Bu) HLMs. The apparent <i>K</i><sub>m</sub> values metabolite...
The present study describes a novel integrated approach for rapid analysis of reactive metabolites with linear ion trap mass spectrometer (LTQ). In this approach, an isotope pattern-dependent scanning method was applied to the data acquisition glutathione (GSH)-trapped metabolites. Recorded full-scan MS and MS/MS sets were further processed neutral loss filtering, product extracted chromatographic search protonated molecules spectra GSH adducts. To evaluate effectiveness reliability adducts...