Jan 22

Little to LARGE: LC-MS/MS peptide method development for small molecule specialists

The development of LC-MS/MS methods for the quantitation of large molecules within biological matrices can help to overcome some of the challenges associated with immunoassay-based analyses. For example, the need to raise new antibodies against novel analytes, poor specificity due to cross reactivity with similar compounds, and for radioimmunoassays the additional safety considerations.

Glucagon peptide2

LC-MS/MS method development

However, LC-MS/MS method development can be demanding within itself, and large molecule development offers additional challenges to those commonly encountered with small molecule analysis. For example, sensitivity is split between multiple charge states, traditional extraction techniques deplete (rather than enrich) large molecules, heavy labelled internal standards may be unavailable, and non-specific binding is prevalent. In addition, large molecules are often unstable in biological matrices, necessitating the development of enhanced sample handling procedures. Furthermore, for large molecule biomarkers, endogenous level analysis creates additional complications, as the merits of alternative quantitative strategies, such as standard addition, surrogate matrix and surrogate analyte approaches, must be considered.


LC-MS/MS peptide method development for small molecule specialists

At the recent European Bioanalysis Forum (EBF) Open Symposium, James Howard, Scientist at LGC presented on “Little to LARGE: LC-MS/MS peptide method development for small molecule specialists“.  We are pleased to announce that we are hosting a webinar on the topic, so for those of you that were unable to attend the EBF Open Symposium and would like to learn more on this topic can register for the webinar.

Register >>> 

Using glucagon, a notoriously difficult to quantify endogenous hormone, as a model peptide and ibuprofen as a model small molecule, James Howard, Scientist at LGC, will cover the following during the webinar:

  • Demonstrate some of the differences in their quantitation
  • Discuss a range of possible solutions to the challenges
  • Compare the performance of the resulting LC-MS/MS glucagon method against established immunoassays using clinical samples.
  • Q&A

Date: Wednesday 3 February 2016
Time: 2:30pm – 3:00pm GMT

Register >>> 



Author: James Howard, Scientist, Drug Development Services, LGC


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