单样,多原子质谱法用于研究药物毒性的机制
bioRxiv : the preprint server for biology
|March 3, 2025
概括
对于急性淋巴细胞白血病 (ALL),L-asparaginase (ASNase) 是有前途的,但对于成年人来说过于有毒. 这项研究使用了多原子分析来确定涉及ASNase毒性的途径,并提出了更安全的药物开发的潜在策略.
科学领域:
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
- 毒理学 毒理学 毒理学
背景情况:
- 治疗指数差是药物开发失败的主要原因之一.
- L-阿斯巴拉金酶 (ASNase) 对儿科急性淋巴细胞白血病 (ALL) 有效,但在成人中表现出显著的毒性.
研究的目的:
- 探索ASNase毒性背后的机制.
- 确定减轻ASNase毒性的潜在目标,同时保持其有效性.
主要方法:
- 在ASNase注射后,小鼠血的多原子分析 (代谢学,脂质学,蛋白质学).
- 利用精简的,三合一的LC-MS/MS工作流来针对1625多个分析物的有针对性的分析.
- 纵向采样和对剂量依赖反应的分析.
主要成果:
- 代谢物,脂质和的剂量依赖调节,汇聚在包括抗氧化,炎症,自和细胞死亡在内的途径上.
- 确定了与ASNase毒性相关的特定分子特征.
结论:
- ASNase 毒性与特定的生物途径有关.
- 抑制这些已识别的途径可能提供一种减少ASNase毒性和改善其治疗窗口的策略.
- 开发的多原子工作流是有效的药物毒性机制阐明.
更多相关视频
07:55Integrated Cell Manipulation Platform Coupled with the Single-probe for Mass Spectrometry Analysis of Drugs and Metabolites in Single Suspension Cells
Published on: June 21, 2019
5.7K
07:37An Integrated Raman Spectroscopy and Mass Spectrometry Platform to Study Single-Cell Drug Uptake, Metabolism, and Effects
Published on: January 9, 2020
9.4K
相关概念视频
Mass Spectrometry: Overview
Mass spectrometry is an analytical technique used to determine the molecular mass and molecular formula of a compound. The basic principle of mass spectrometry is to generate ions from the analyte molecule and measure these ion abundances against their molecular mass. One common type of ionization, known as electron ionization or EI, bombards the analyte molecules in the gas phase with high-energy electron beams. The electron beams displace an electron from the molecule and leave behind a...
MALDI-TOF Mass Spectrometry
Mass spectrometry is a powerful characterization technique that can identify and separate a wide variety of compounds ranging from chemical to biological entities, based on their mass-to-charge ratio (m/z). The instruments that allow this detection, known as mass spectrometers, have three components: an ion source, a mass analyzer, and a detector. These spectrometers differ based on the nature of their ion source and analyzers.Matrix-assisted laser desorption ionization (MALDI) is a commonly...
Peptide Identification Using Tandem Mass Spectrometry
Tandem mass spectrometry, also known as MS/MS or MS2, is an analytical technique that employs two mass analyzers. Essentially it is a series of mass spectrometers that helps isolate a particular biomolecule and then helps study its chemical properties.
This technique helps gather information regarding the protein from which the peptide was obtained and to study the peptides’ amino acid sequence. Identifying peptides from a complex mixture is an important component of the growing field of...
This technique helps gather information regarding the protein from which the peptide was obtained and to study the peptides’ amino acid sequence. Identifying peptides from a complex mixture is an important component of the growing field of...
Mass Spectrometry: Complex Analysis
Mass spectrometry is an important technique for the identification of pure compounds. However, it has some limitations for the analysis of complex mixtures, often due to excessive fragmentation making the spectrum too complicated to decipher. Mass spectrometry can be combined with suitable separation methods in sequence, forming hyphenated methods, which are useful in the analysis of complex mixtures.
GC–MS is a powerful hyphenated method commonly used in forensics and environmental...
GC–MS is a powerful hyphenated method commonly used in forensics and environmental...
Tandem Mass Spectrometry
Tandem mass spectrometry is a technique that uses multiple mass analyzers in series to obtain a higher selectivity and reduce chemical noise during analyte detection. Instruments with multiple analyzers separated by an interaction cell enable secondary fragmentation and selected study of the fragment ions.Secondary fragmentations occur in the interaction cell and can be induced by various factors. Fragmentation induced by collision with inert gases, such as N2, Ar, He, etc., is called...
Therapeutic Drug Monitoring: Drug Analysis Methods
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood or body tissues to tailor drug therapy effectively. This monitoring is critical for managing drugs with narrow therapeutic indices like digoxin and phenytoin, ensuring they are both safe and effective. For instance, monitoring theophylline levels in asthma patients involves precision and sensitivity to adjust doses according to individual responses to therapy, ensuring efficacy and...
