The increase in scientific advances pushes fields that use older models to strive to integrate these newer techniques and machines into general practice. The legal field has a responsibility to do this as to give the people a fair trial. In respect to forensic toxicology, gas chromatography-mass spectrometry is the method of choice. Liquid chromatography-mass spectrometry however has become increasingly important in forensic toxicology as it provides clear advantages over its alternative. About 70% of routine samples in the toxicological laboratory can be handled by LC. LC combined with MS allows for valuable analytical contributions to be applied to a much wider array of compounds. Research over the past decades have seen many suitable interfaces between LC and MS leading itself past the experimental phase and has seen widespread success mainly in colleges. This is in contrast with regards to the usage LC-MS has received over the past years. Usage is relatively low compared to GC-MS. This can be attributed to LC-MS instruments costing more than half the cost of GC-MS instruments while GC-MS still obtain the same outcome LC-MS instruments receive.
LC-MS when combined together creates three major difficulties that must be solved and improved on in future iterations. The apparent low-rate incompatibility from the column to the MS, the solvent composition (non-volatile mobile phase additives), and when MS cannot analyze polar, ionic, nonvolatile, high molecular mass, and thermally labile analytes. Several solutions have been formulated however only three general concepts have seen widespread use. The first set is nebulization of the column effluent, removal of the mobile phase constituents, and vaporization of the analytes followed by ionization. The second set is direct ionization from a microliter effluent stream continuously deposited on a target. The third set is nebulization of the effluent in either an atmospheric-pressure or a reduced-pressure region, desolvation of the droplets, followed by either gas-phase chemical ionization or ion evaporation, thermospray, electrospray, and atmospheric-pressure chemical ionization. The scope of this paper does not allow for even rudimentary explanations for all of these, so I have chosen LC-particle beam-MS, thermospray, and atmospheric pressure chemical ionization as they are relevant to the objectives of this paper. Particle beam interfaces utilizes a particle beam interface to transport and deposit desolvated analyte molecules onto a target surface that is bombarded by a primary beam of massive multiply charged cluster ions to generate secondary ions for mass analysis. The particle beam interface generates database searchable electron ionization and chemical ionization mass spectra of volatile or semi-volatile compounds. PB’s weaknesses lie in the limited scope of compounds that can be ionized and is generally confined to small molecules.
Thermospray gives two advantages: reduces the amount of solvent that enters the mass spectrometer vacuum; ionizes the solute. While eluting, the liquid is sprayed through a specific heated ion chamber so that a jet of vapor is produced. This vapor gains electric charge, increasingly so until free ions are produced. This technique suffers from stable signal intensity in part due to sensitivity with temperature and other instrument parameters. However, this method solves the flow rate and ionization of non-volatile and thermally labile compounds issues. This method was the most widespread until the invention of atmospheric pressure ionization. While most of these applications are very limited in scope atmospheric pressure ionization instruments are mostly universal, long lasting, highly sensitive and have the advantage of multiple charge ionization. The atmospheric pressure chemical ionization technique the eluent is nebulized (converts liquids into a fine mist) from a capillary. Desolvation is enabled and forms the vapor of the analyte and solvent molecules. At the same time a discharge electrode ionizes solvent molecules, which transfers a charge to the analyte. The ions are then sampled from the atmospheric pressure region with high vacuum through a system of nozzle and skimmers, sometimes with a counter-current drying gas. This technique has many similarities to the thermospray method except that has easy operability and has less issues with temperature. APCI is very sensitive with analytes that have moderate polarity and molecular mass. Since the technique uses chemical ionization, it provides no informative fragmentation.