The Evolution of Today’s LC/MS Techniques

Liquid chromatography/mass spectrometry (LC/MS) has become an indispensable analytical technique across many important application areas. These include pharmaceutical, environmental, forensic, clinical, and medicinal chemistry to name a few. In the early LC/MS days of the late 1970’s it was a struggle to determine how best to introduce HPLC condensed phase liquids into the high vacuum ion source of the mass spectrometer. This dilemma was portrayed by the cartoon published by Dr. Patrick Arpino in 1981 which called this a ‘Difficult Courtship’.
This presentation will summarize how LC/MS techniques evolved from the Direct Liquid Introduction (DLI), Particle Beam and Thermospray approaches based upon the above. The early techniques were replaced by creating gas-phase ions at atmospheric pressure and introducing them into the ion optics of an atmospheric pressure ionization (API) mass spectrometer via atmospheric pressure chemical ionization (APCI) or electrospray ionization (ESI). These two latter ionization techniques have revolutionized the means of doing LC/MS across a wide array of modern mass spectrometer technologies ranging from simple benchtop single quadrupoles (LC/MS), to tandem triple quadrupoles (LC/MS/MS), quadrupole/time of flight (LC/QTOF) and orbitrap mass spectrometers with high mass resolution. A variety of interesting applications will be shown along with some recent research to develop a breath analysis technique amenable to a mobile laboratory for roadside breath analysis for marijuana using a single quadrupole LC/MS system.