Application of the Liquid Chromatography/Mass Spectrometer/Mass Spectrometer (LC/MS/MS) Instrument

Application of the Liquid Chromatography/Mass Spectrometer/Mass Spectrometer (LC/MS/MS) Instrument

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LC/MS/MS Instrument Arrives at RJLG

Recently obtained by the RJ Lee Group, the liquid chromatography/mass spectrometer/mass spectrometer (LC/MS/MS) is an instrument with exceptional capability for both qualitative and quantitative analysis. It has remarkable sensitivity and is capable of providing fast and accurate identification of targeted compounds of interest.

In many instances the instrument will be able to provide the following:
• Lower reporting limits
• Greater specificity
• Faster analysis times
• Simplify sample preparation procedures
• Improved problem solving capabilities

Mass Analyzers

This instrument takes advantage of two separate mass analyzer designs.

The first is the triple quadrupole configuration, which supports eight different types of mass spectrometry experiments. There are three quadrupole sections in the instrument. In some modes of operation, the first quadrupole (Q1) permits the operator to select a specific ion for a compound. The second quadrupole (Q2) is used for fragmentation of that selected ion. The third quadrupole (Q3) can either be used to monitor a specific ion from the second fragmentation process, or to collect the entire mass spectrum resulting from the Q2 fragmentation of the Q1 selected ion. One can imagine several experiments that can be used for qualitative and quantitative analysis. Among these is the ability to perform multiple reaction monitoring (MRM) measurements for quantitative determinations with exceptionally low reporting limits.

The second mass analyzer design simply changes the electronic configuration of Q3 to make it function as a linear ion trap (LIT). Conventional ion trap systems are plagued by space charge effects. These are caused when the electrons emitted by the cathode are repulsed by the cloud of electrons near the cathode itself. The maximum ion density in the trap must be controlled and limited in order to reduce this occurrence. This will decrease premature ejection of the ions and the loss of mass resolution. The LIT permits the trapped ion density to increase significantly, causing substantial increases in sensitivity. Six additional mass spectrometry related experiments can be performed when the instrument is operated in the LIT mode.


The LC/MS/MS only works if a target compound can be ionized before it is introduced to the instrument. The ionization processes most commonly used are electrospray (ESI), or one if its variants, and atmospheric pressure chemical ionization (APCI). Both are readily used for samples introduced by a liquid chromatograph (LC) or direct liquid infusion (DLI). Both are ionization processes that occur at atmospheric pressure rather than in a vacuum as in conventional gas chromatography/mass spectrometry (GC/MS) using electron ionization (EI).

Gas chromatography, another method used for identifying compounds, requires a target compound to have some degree of volatility, and to be stable under elevated thermal conditions during the analysis process. This limits the use of GC to the analysis of less than 3% of the known chemicals in the Chemical Abstracts Registry. Liquid chromatography (LC), conversely, is potentially amenable to any compound that can be dissolved in an aqueous or organic solvent. Liquid Chromatography consequently becomes a powerful separation and sample introduction technique to a mass spectrometer. This enables the analysis of a broad range analytes, and subsequently, a broad range of applications.

Instrument Applications

Applications of LC/MS/MS are extensive. A good resource for applications can be found in the vendor catalogs of the LC columns. Many of these vendors produce chromatograms of families of compounds such as nitrosamines, pesticides, drugs of abuse, pharmaceutical byproducts, carbohydrates, antibiotics, aflatoxins, peptides and proteins, explosives, aldehydes and ketones, to name a few.

A successful analysis depends in part in isolating the target analytes from the sample matrix and performing the chromatographic separation. In many cases, sample cleanup can be simplified by taking advantage of the power of the instrument to perform selective analysis of the ion(s) that indicate the presence of the target analyte(s) by using the MS/MS function (a mass spectrometer within a mass spectrometer). The analytical technique can be applied to samples originating from industrial hygiene monitoring, environmental sampling, fermentation broths, growth media, agriculture industry, process control, biomedical analyses, and countless others.

For more information on the LC/MS/MS, please click the button below or call (509.545.4989).