In quadrupole mass spectroscopy, a type of mass analyzer known as quadrupole mass spectrometer (QMS) is used. The spectrometer is also referred to as a quadrupole mass analyzer or quadrupole mass filter.
This article explains the quadrupole arrangement, working principle, and instrumentation in quadrupole mass spectroscopy. The way the electric field works in the quadrupole system is also described. Lastly, we have also discussed the differences between a single quadrupole and a triple quadrupole mass spectrometer.
So, without any further delay, dive into the article and let us start reading all about quadrupole mass spectroscopy!
What is quadrupole mass spectroscopy? – Definition
Quadrupole mass spectroscopy is an analytical technique that separates and analyses ionic species in a chemical compound.
Quadrupole is a type of mass analyzer used in the mass spectrometer. It is an instrument that separates ions on the basis of their mass-to-charge ratios (m/z). The separation of ions in a quadrupole analyzer depends on the stability of their trajectories. These trajectories are recorded under the influence of oscillating electric fields applied to the rods.
Quadrupole mass spectrometers (QMS) come in various formats, such as a single quadrupole mass spectrometer and a triple quadrupole mass spectrometer.
QMS can be employed in quantitative and targeted applications. It is also used to measure or scan ions in a mixture according to their m/z values.
What is the basic working principle of quadrupole mass spectroscopy?
A radio frequency (RF) voltage is applied between the electrically connected opposing rod pairs. The superimposition of a direct current (DC) voltage on the RF voltage impacts the ions. The ions take an irregular, oscillatory trajectory as they pass through the 3-D channel among the rods.
In a quadrupole mass analyzer, four parallel cylindrical metal rods are positioned at equal distances from the central axis. These rods are charged with direct current (DC) or radio frequency (RF) voltages arranged as opposite pairs of rods with like charges. As ions pass through the RF field, oscillating electric fields are employed to stabilize or destabilize them selectively.
Important terminology:
- Stable trajectory: Ions of a selected mass-to-charge ratio forms a stable trajectory. This allows the selected ions to reach the detector.
- Unstable trajectory: Ions with different mass-to-charge ratios form an unstable trajectory, collide with the rods and eventually radially get expelled from the analyzer.
- Selection of ions: To select the ions of a particular m/z ratio, the voltage and polarity applied to the rods is adjusted.
What is a quadrupole mass spectrometer?
A quadrupole mass analyzer is one of the components of a mass spectrometer. The mass spectrometer containing the quadrupole system as a mass analyzer/filter is known as the quadrupole mass spectrometer.
While taking a holistic view at a mass spectrometer, the configuration of the quadrupole mass analyzer is also taken into account.
Instrumentation:
The typical QMS consists of three parts: 1) ion source, 2) quadrupole mass analyzer and 3) detector.
1. Ion source
The sample to be analyzed is subjected to ionization in the ion source.
The ions are then passed through the mass analyzer by applying an electrical or magnetic field.
There are generally two ionization methods that are employed in QMS, as per the sample under investigation.
I) Electron Ionization (EI)
- In this method, the sample is first vaporized inside the ion source.
- Ionization is carried out via a beam of electrons having sufficient energy of approximately 70 eV.
- EI facilitates structural determination such that the final mass spectrum consists of fragment and molecular ions.
- This method is suitable for analyzing relatively less volatile, non-polar sample components. In this way, it is limited to using thermally stable compounds as analytes.
- EI is thus not suitable for ionic compounds.
II) Electrospray ionization method (ESI)
- It is a soft-ionization method that produces few in-source fragment ions.
- A sample in solution form is passed through a metal capillary with a high potential of (4-5kV).
- This converts the sample solution into tiny droplets. These droplets then carry a charge at the time of exiting the capillary. The droplets disappear as the solvent evaporates, leaving behind charged analyte molecules.
- An ESI mass spectrum generally contains multiply-charged ions for large analytes such as proteins.
- This method works well for large as well as small molecules. It analyzes bio- or synthetic polymers, polar molecules and even ionic compounds.
2. Quadrupole mass analyzer
- The function of the quadrupole mass analyzer is to separate ions as per their mass-to-charge (m/z) ratios.
- As the term quadrupole implies, it can be inferred that QMS comprise four cylindrical rods arranged parallel to one another.
3. Detector
- The detector helps record the current produced or charge induced as the ion hits the surface.
QMS is often coupled with other techniques, such as HPLC or gas chromatography, to identify and analyze various analytes present in a sample.
In GC/MS or LC/MS, gas or liquid chromatography is performed to chromatographically separate compounds before being introduced to the ionization source and mass spectrometers.
How does the quadrupole field works?
A demonstration of an electric quadrupole shows two positive and two negative charges placed alternately on the corners of a square formed by quadrupole rods. This arrangement contains two dipoles with dipole moments of equal magnitude but opposite directions.
The monopole and dipole moment of this system is zero, but the electric field is not zero. A fluctuating electric field results due to the voltages between the rods. The electric field oscillates between the rods at a particular frequency.
- Ions with a high mass-to-charge ratio can pass between the positive rods.
- Ions with a low mass-to-charge ratio can pass between the negative rods.
- The ions with a narrow mass-to-charge ratio can pass through the rods if voltages are correctly selected.
What is the difference between a single quadrupole mass spectrometer and a triple quadrupole mass spectrometer?
The differences between a single quadrupole and triple quadrupole MS are given in the table drawn below.
| Single quadrupole mass spectrometer | Triple quadrupole mass spectrometer |
| This configuration comprises a single mass analyzer/filter between the reaction/collision cell and the detector. | This type of MS contains two quadrupole mass analyzers separated via a collision cell, one placed before and the other after the cell. A triple quadrupole mass analyzer is also known as a tandem quadrupole mass spectrometer. |
| This type can only measure ions formed in the instrument source. | First quadrupole mass analyzer selects precursor ions which are then fragmented inside the collision cell. |
| These ions can be fragment ions or molecular ions that are formed as a result of in-source fragmentation. | The fragmentation occurs through a process called collision-induced dissociation (CID). |
| Selected Ion Monitoring (SIM) The most selective mode used to operate a single quadrupole MS is selected ion monitoring. This variant is limited in terms of specificity. Single quadrupole MS is not capable of providing sufficient structural information. In this mode, quadruple is subjected to a fixed set of DC and RF voltages. Merely a single m/z can pass through, whereas ions having different m/z get filtered out. |
Multiple Reaction Monitoring (MRM) Multiple reaction monitoring is the common mode selected to operate a triple quadrupole MS. This mode is used for quantitative analysis and allows enhanced selectivity and sensitivity. The first quadrupole Q1 filters the precursor ion of interest. Ions of different m/z cannot filter through Q1. The optimization of the collision cell is done to generate a characteristic product ion. That results from a collision between a precursor ion and a neutral gas, such as argon. This process is known as Collision-Induced Dissociation (CID). The characteristic product ion is passed to the second quadrupole, where ions of specific m/z can pass. The rest of the product ions are then filtered out. |
Single quadrupole and triple quadrupole MS detect many transitions of SIM and MRM, respectively. This feature allows quantitation of various targeted analytes within a single experiment.
Why is quadrupole mass spectroscopy important? – Applications
Just like any other form of mass spectroscopy, quadrupole MS is used for qualitative and quantitative analysis in:
- Research and development
- Drug testing
- Pharmaceutical industry
- Determining food contamination
- Protein identification
- Carbon dating to study the age of minerals and rocks
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References
1. Mellon, F. A. 2003. ‘MASS SPECTROMETRY | Principles and Instrumentation.’ in Benjamin Caballero (ed.), Encyclopedia of Food Sciences and Nutrition (Second Edition) (Academic Press: Oxford).
2. Thomas, Stefani N. 2019. ‘Chapter 10 – Mass spectrometry.’ in William Clarke and Mark A. Marzinke (eds.), Contemporary Practice in Clinical Chemistry (Fourth Edition) (Academic Press).
