Applications of Mass Spectrometry in Drug Development Science
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 chromatographic 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.
KeywordsQualitative and quantitative mass spectrometry Small molecules and protein biopharmaceuticals Higher-order structure (HOS) elucidation Hydrogen/deuterium exchange mass spectrometry (HDX-MS) Pharmacokinetics and mass spectrometry
- Herman JL, Edge T, Majors RE (2012) Theoretical concepts and applications of turbulent flow chromatography. LCGC North America 30(3):200–214Google Scholar
- Hoffmann ED, Stroobant V (2007) Mass spectrometry: principles and applications. Wiley, Hoboken, NJ; Chichester: John Wiley [distributor]Google Scholar
- Houde DJ, Berkowitz SA (2015) Biophysical characterization of proteins in developing biopharmaceuticals. D. J. H. A. Berkowitz. Elsevier, AmsterdamGoogle Scholar
- Hunt DF, Coon JJ, Syka JEP, Marto JA (2005). Electron transfer dissociation for biopolymer sequence analysis. US 11079147Google Scholar
- Korfmacher WA, Palmer CA, Nardo C, Dunn-Meynell K, Grotz D, Cox K, Lin CC, Elicone C, Liu C, Duchoslav E (1999) Development of an automated mass spectrometry system for the quantitative analysis of liver microsomal incubation samples: a tool for rapid screening of new compounds for metabolic stability. Rapid Commun Mass Spectrom 13(10):901–907CrossRefPubMedGoogle Scholar
- Li Y, Shin YG, Yu C, Kosmeder JW, Hirschelman WH, Pezzuto JM, van Breemen RB (2003) Increasing the throughput and productivity of Caco-2 cell permeability assays using liquid chromatography-mass spectrometry: application to resveratrol absorption and metabolism. Comb Chem High Throughput Screen 6(8):757–767CrossRefPubMedGoogle Scholar
- Little TA (2015) Method validation essentials, limit of blank, limit of detection, and limit of quantitation. Biopharm Int 28(4):48–51Google Scholar
- Tao L, Ackerman M, Wu W, Liu P, Russell R (2011) Characterization of impurities and degradants using mass spectrometry. Wiley, HobokenGoogle Scholar