Abstract
Mass spectrometry (MS) offers the capability to identify, characterize and quantify a target molecule in a complex sample matrix and has developed into a premier analytical tool in drug development science. Through specific MS-based workflows including customized sample preparation, coupling to liquid chromatography and different ionization principles, both qualitative and quantitative analysis of small and large drug compounds can be achieved at an unprecedented sensitivity.
Here, we review the basic principles of MS and tandem MS, including ionization, mass analysis and detection, as well as fragmentation techniques and coupling of MS to chroma-tographic separation. As the structural integrity of protein drugs during purification, formulation and delivery is of critical importance to ensure drug efficacy and safety, an overview over current approaches for primary and higher-order structure analysis of proteins by mass spectrometry will be given as well as related workflows for quantitative MS analysis. Established “top-down” and “bottom-up” protein analyses with MS will be recapitulated, and the use of emerging technologies such as hydrogen/deuterium exchange mass spectrometry (HDX-MS) for higher-order protein structure analysis will be discussed.
Here, we review the basic principles of MS and tandem MS, including ionization, mass analysis and detection, as well as fragmentation techniques and coupling of MS to chroma-tographic separation. As the structural integrity of protein drugs during purification, formulation and delivery is of critical importance to ensure drug efficacy and safety, an overview over current approaches for primary and higher-order structure analysis of proteins by mass spectrometry will be given as well as related workflows for quantitative MS analysis. Established “top-down” and “bottom-up” protein analyses with MS will be recapitulated, and the use of emerging technologies such as hydrogen/deuterium exchange mass spectrometry (HDX-MS) for higher-order protein structure analysis will be discussed.
| Original language | English |
|---|---|
| Title of host publication | Analytical Techniques in the Pharmaceutical Sciences |
| Editors | Anette Müllertz, Yvonne Perrie, Thomas Rades |
| Number of pages | 36 |
| Publisher | Springer Publishing Company |
| Publication date | 2016 |
| Pages | 253-289 |
| Chapter | Applications of Mass Spectrometry in Drug Development Science |
| ISBN (Print) | 978-1-4939-4027-1 |
| ISBN (Electronic) | 978-1-4939-4029-5 |
| Publication status | Published - 2016 |
| Series | Advances in Delivery Science and Technology |
|---|---|
| ISSN | 2192-6204 |