TY - CHAP

T1 - Analytical Techniques in the Pharmaceutical Sciences

AU - Leurs, Ulrike

AU - Mistarz, Ulrik Hvid

AU - Rand, Kasper Dyrberg

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

M3 - Book chapter

SN - 978-1-4939-4027-1

T3 - Advances in Delivery Science and Technology

SP - 253

EP - 289

BT - Analytical Techniques in the Pharmaceutical Sciences

A2 - Müllertz, Anette

A2 - Perrie, Yvonne

A2 - Rades, Thomas

PB - Springer Publishing Company

ER -