Time Of Flight – Mass Spectrometers

ToF-MS – also known as Time of Flight Mass Spectrometers measure the m/z of ions by calculating its time of flight in a high vacuumed free-drifting region at particular velocity at fixed distance. Figure 3.11 illustrates this method clearly. The ToF-MS runs on the basic principle of kinetic energy i.e. the energy of motion. The kinetic energy of ion in this method is therefore dependent on mass (m) and velocity (v).

E= 1/2mv2

The energy (E) is therefore equivalent to the ion charge (z) and the voltage applied (v) which is used to accelerate the ions in the drift region inside the MS.

zV=1/2mv2

The velocity (v) would not change in the vacuumed drift region and can also be found from the (d) i.e. the path length of the ion and their flight time (t) by:

V=(d/t)

If we substitute the velocity and rearrange the equation, the time of flight of the ion would be expressed as:

T=d[2V/(m/z)]1/2

The ‘d’ i.e. the path length and the ‘v’ voltage are fixed and directly related to the manufacturer’s design and the setting of specific instruments.

So, the values are constant (c) which are also specific while pertaining to the instrument parameters and their specificity. A simple equation tells that the square root of the mass of an ion is directly related with that ion’s ToF in free drift area:

T=c(m/z)1/2

Thus, the mass can be found by the time of flight of an ion. For obtaining accurate readings, the ions for the particular compound should enter the drift area at the same time.

The ions which are formed by electron ionization or laser ionization are transmitted to ToF spectrometer via electrical potential having pulsations of 1-10 ns. This pulsation as well as a focusing of ions before they enter the spectrometer makes sure that the ions travel through a drift free area simultaneously with same energies. Their resolution is further made better by the reflection of ions along the drift passage which expands the difference in flight time. This also balances the difference that is observed with ions having the same m/z but different kinetic energy. The lengths of the ion paths are increased till 2 meters having flight time ranging from 5 to 100 µs which leads to fast and correct measurements. This also allows T0F-MS instruments to give a resolution of 20,000 as well as a dynamic mass range of 500 kDa.

ToF instruments are also coupled with liquid chromatography which is used to analyze cocaine, cocaethylene and Benzoylecgonine in oral fluids. The instrument’s sensitivity is set at 1 ng/mL for LoDs in all three parts which have as little as 100 mL of saliva. The G-ToF-MS is used to quantify and confirm the sub-nanogram levels of bromazepam, diazepam and nordiazepam which are extracted from blood. The reported levels are 50 times lower than the usually used conventional G-Q-MS techniques. The sensitivity of ToF-MS allows the laboratories to have smaller sample aliquots which are very important while doing tests on limited specimens or where multiple assay tests are to be done. The better stability also enhances the detection window of these drugs which is important to analyze low dose, quickly metabolized drugs like lysergic acid diethylamide (LSD).

Many studies are conducted to evaluate the ToF for screening and identification of compounds which range only on mass determination. These studies were done on many compounds like opiates, benzodiazepines, sleep medications, antidepressants and beta blockers. Even though, their results showed that accurate mass measurements of ToF were not enough to recognize and positively identify the compounds, but they very well showed the capability to identify the unknown compounds’ general formula. Therefore, this application is very useful while testing unknown metabolites or new drugs whose references are not available.

Even though, the ToF instruments are not used for routine analysis, their usage as a confirmation technique is quite promising. Recent publications which have analyzed ∆9-tetrahydrocannabinol and 11-Nor-9-carboxy-∆9-tetracannabinol compounds in oral fluid as well as low concentration benzodiazepines in rape cases show ToF-MS in forensic sciences. There is continuous improvement in accurate measurement of a compound’s mass (<3 ppm) and its resolution (< 20,000). Moreover, the coupling of ToF mass spectrometer with the MS-MS methods ensures better identification and a bright future for the technological advancements in the field of forensic sciences.

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