GEN-MKT-18-7897-A
Apr 25, 2024 | Blogs, LC, Pharma | 0 comments
Read time: 3 minutes
The dream state
If we lived in an ideal world, it would be possible to unambiguously identify metabolites using a single analytical experiment. This analytical technique would need to be efficient and easily generate the information needed from a routine assay that is also robust, enabling confident decision-making during drug discovery.
At SCIEX, we believe that metabolite identification using the ZenoTOF 7600 system gets close to this dream state.
The science
Currently, the starting point for metabolite identification is typically a liquid chromatography with high-resolution mass spectrometry (LC-HRMS) experiment using fragmentation to allow structural elucidation of the analyte. The “go to” fragmentation technique is collision-induced dissociation (CID), which provides a wealth of information but doesn’t always allow for explicit identification of the metabolite.
The ZenoTOF 7600 system offers both CID and electron-activated dissociation (EAD) fragmentation, which complement each other. EAD can cause ions in an LC-MS/MS experiment to fragment in locations that are different from where they fragment with CID, providing scientists with additional information in a single experiment.
For metabolite identification, this could mean confidently identifying a single site of metabolism instead of two or three possible sites using CID only and removing the need for additional safety testing.
The evidence
A recent peer-reviewed paper, Electron activated dissociation – a complementary fragmentation technique to collision-induced dissociation for metabolite identification of synthetic cathinone positional isomers – ScienceDirect, reported the following when researching the metabolism of new psychoactive substances (NPS):
“The tentative structural elucidation of metabolites of NPS formed using in vitro models is typically carried out using liquid chromatography combined with high-resolution tandem mass spectrometry (LC-HRMS2) with collision-induced dissociation (CID) as a fragmentation method. However, the thermally excited ions produced with CID may not be sufficient for unambiguous identification of metabolites or their complete characterization. Electron-activated dissociation (EAD), a relatively new fragmentation approach that can be used to fragment singly charged ions, may provide complementary structural information that can be used to further improve the confidence in metabolite identification.”
“The EAD product ion mass spectra showed different fragmentation patterns compared to CID, where unique and abundant product ions were observed in EAD but not in CID. More importantly, certain EAD exclusive product ions play a significant role in structural elucidation of some metabolites. These results highlight the important role that EAD fragmentation can play in metabolite identification workflows, by providing additional fragmentation data compared with CID and, thus, enhancing the confidence in structural elucidation of drug metabolites.”
To learn more about how EAD could be used in your laboratory, this webinar may be of interest: Discover how Bristol-Myers Squibb uses electron-activated dissociation (EAD) to confidently identify drug metabolites and localize site of metabolism (theanalyticalscientist.com). In the webinar, Ming Yao, Principal Scientist, CPPDB, at Bristol-Myers Squibb, discussed how the additional information from EAD can help in confident localization and identification of metabolites compared to CID alone. The study demonstrated that these fragments can be crucial to locating the metabolic modification sites, such as conjugations.
For more information on the options SCIEX offers for metabolite identification, please speak to your account manager or visit our web page on Comprehensive Metabolite Identification | SCIEX.
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has gained significant attention in the clinical laboratory due to its ability to provide best-in-class sensitivity and specificity for the detection of clinically relevant analytes across a wide range of assays. For clinical laboratories new to LC-MS/MS, integrating this technology into their daily routine operations may seem like a daunting task. Developing a clear outline and defining the requirements needed to implement LC-MS/MS into your daily operations is critical to maximize the productivity and success of your clinical laboratory.
In today’s rapidly evolving food industry, the role of food testing laboratories has never been more critical. Ensuring the safety, quality, and authenticity of food products is paramount, and this responsibility falls heavily on the shoulders of laboratory managers. The economics of food testing—encompassing everything from high-throughput pesticide screening to advanced research on alternative protein sources—plays a pivotal role in shaping the operational efficiency and financial health of these laboratories.
Imagine having a tech expert at your fingertips to solve computer issues or a fitness trainer guiding you through workouts from the comfort of your home. In today’s fast-paced world, the ability to provide and receive service and support remotely is no longer a luxury but a necessity. Whether it’s troubleshooting a software issue, repairing a device, offering customer assistance, or enjoying the convenience of telehealth as a private individual, remote capabilities have revolutionized how businesses operate and how individuals get help
Posted by
You must be logged in to post a comment.
Share this post with your network