CHEM 420: Special Topics in Analytical Chemistry - Mass Spectrometry
Instructor: Dr. Richard W. Smith
Mass Spectrometry (MS) (PDF) is a powerful analytical technique and indispensable tool in chemistry, biochemistry, biology, pharmacy, environment, and medicine. No student, researcher, or practitioner in these disciplines can really get along without a substantial knowledge of mass spectrometry.
This course provides students with the most up-to-date review of the concepts, technology, and the qualitative and quantitative applications of mass spectrometry, as well as the opportunity to visit one of the leading MS manufacturers, ABSciex.
Every experiment starts with an unknown (bio)chemical species; this must be converted into an ion with or without fragmentation and then separated and detected. How this is accomplished and what it can tell us will be thoroughly explored in this course.
1. What is mass spectrometry? What information does mass spectrometry provide?
Mass spectrometry measures the molecular mass of any (bio)chemical species, as well as how the atoms are connected (structural elucidation).
- Molecular weight determination:
- For large biomolecules, molecular masses can be measured to within an accuracy of 0.01%, that is, within a 4 Daltons (Da) or atomic mass units (amu) error for a sample of 40,000 Da. This is sufficient to allow minor mass changes to be detected, for example, the substitution of one amino acid for another or a post-translational modification.
- For small organic molecules, the molecular mass can be measured to within an accuracy of 2 ppm or less, which is sufficient to confirm the molecular formula of a compound, that is, the number of C's, H’s, O’s, N’s, or any other atoms (and their isotopes) in the periodic table. This information is a standard requirement for publication in the scientific literature.
- Structure elucidation employing tandem MS (MS/MS and MSn):
- Structural information can be generated using certain types of mass spectrometers, usually those with multiple analyzers which are known as tandem mass spectrometers. This is achieved by fragmenting the ion inside the instrument and analyzing the products generated. This procedure is useful for the structural elucidation of organic compounds, (bio)chemical species such as peptides or oligonucleotides.
Moreover, mass spectrometers can be coupled to chromatographic methods, such as gas chromatography or high performance liquid chromatography (and others) to separate complex mixtures before they are introduced to the mass spectrometer.
2. Where are mass spectrometers used?
Mass spectrometers are widely used in industry, academia, and government. The major applications are summarized as follows:
- Biotechnology: The analysis of proteins, peptides (proteomics), oligonucleotides, lipids (lipidomics), and carbohydrates.
- Pharmaceutical: Drug discovery, combinatorial chemistry, pharmacokinetics, and drug metabolism (metabolomics).
- Clinical: Neonatal screening, haemoglobin analysis, and drug testing.
- Environmental: Water quality and food contamination.
- Geological: Oil composition.
- Space exploration: Many of NASA's premier missions (Galileo, Cassini, Mars Curiosity Rover, etc.) have mass spectrometers as part of their payload.
- Quantitative analysis: MS (coupled to chromatography) is the gold standard used to determine how much of an analyte is present in a sample. For example:
- Steroids and other drugs of abuse in athletes.
- Toxic environmental contaminants, such as polycyclic aromatic hydrocarbons (PAH’s), polychlorinated biphenyls (PCB’s), and dioxins.
- Pharmaceuticals and their metabolites in humans.
- Determining metals at ppq (parts per quadrillion) levels in water samples.