This is the second of a three-part series on Thermo Fisher Scientific analytical instrument solutions for metabolite identification in the small molecule DMPK drug development process. If you missed part one, catch up here: Speed up the drug development process …
Metabolite identification (MetID) using LC-MS instrumentation from in vitro and in vivo studies is a critical part of the drug development process, but having improper tools to assess drug metabolism can lead to serious and costly implications during clinical phases and ꟷ in the worst case ꟷ rejection of an NDI. Fortunately, Thermo Fisher Scientific offers advanced tools to avoid pitfalls related to improper MetID assessment.
Identifying metabolites in challenging matrices shouldn’t be a challenge
To determine the transformation site for metabolites typically requires fragmentation data, making it necessary to obtain fragmentation coverage of all metabolites. However, one of the main challenges in the profiling of drug metabolites is that complex background signals from matrix components can obscure low-level metabolites during data acquisition, making the untargeted fragmentation data acquisition difficult. In this whitepaper, Hackbusch et al. discuss the benefits of using advanced acquisition strategies to exclude unwanted background information and ultimately simplify the data analysis.
Additionally, routine metabolite identification work typically relies on collisional dissociation (HCD or CID) to generate diagnostic fragments. However, in some instances the determination of transformation sites can be challenged if only non-specific fragments are generated. Orthogonal fragmentation modes such as ultraviolet photo dissociation (UVPD) can allows for deeper insight. As an example of this benefit, Figure 1 shows the use of UVPD fragments to determine the localization of an acyl-glucoronide bond for a metabolite of diclofenac, which wasn’t possible from HCD fragmentation data.
Read the complete whitepaper on drug metabolite identification and discover our metabolite identification solutions on the Thermo Fisher Scientific website.
Related information
Blog Part 1 of 3: Speed up Drug Development Process With Fit-for-Purpose Metabolite Identification Solutions
Blog Part 3 of 3: Leveraging LC-MS for Accurate Metabolite Identification (MetID) in Drug Discovery & Development
Blog: Metabolite Identification Solutions Showcased at Great Lakes DMDG 2024 Meeting
You can also find out more about Thermo Fisher Scientific’s cutting edge analytical instruments and software solutions to streamline and speed up any drug development processes in our Pharma & Biopharma Learning Center.
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