Modern instrumental methods in forensic toxicology

Abstract

This article reviews modern analytical instrumentation in forensic toxicology for identification and quantification of drugs and toxins in biological fluids and tissues. A brief description of the theory and inherent strengths and limitations of each methodology is included. The focus is on new technologies that address current analytical limitations. A goal of this review is to encourage innovations to improve our technological capabilities and to encourage use of these analytical techniques in forensic toxicology practice.

Figure 1

Schematic showing resonant ions of selected mass-to-charge ratios being sorted and detected in a quadrupole mass spectrometer (QMS). A constant DC to AC current ratio (AC current produces a radiofrequency field) selects the resonant ion. Source: http://www.chem.vt. edu/chem-ed/ac-meths.html.

Figure 2

Schematic of a Deans Switch. When the solenoid switch is off, the pressure control module (PCM) directs flow from the first column to the flame ionization detector (FID; blue arrows). When the solenoid switch is turned on, the PCM directs flow from the first column onto the second column with detection by a quadrupole mass spectrometer (QMS; red arrows). Source: Agilent Technologies.

Figure 3

Selected ion chromatograms of 1 ng/mL of ?⁹-tetrahydrocannabinol in human plasma extracts produced without (peak A) and with (peak B) the Deans Switch (Agilent Technologies).

Figure 4

Schematic showing a tandem mass spectrometer (MS–MS). In a linear quadrupole instrument, Q1, Q2, and Q3 represent the three tandem quadrupoles. Four different operational configurations are shown: product ion scanning provides structural information (A); precursor ion scanning identifies all compounds producing specific fragments (B); neutral loss scanning screens for compounds producing neutral loss fragments (e.g., m/z 176 for glucuronide conjugates) (C); and selected reaction monitoring monitors targeted analytes and simultaneously monitors multiple transitions (D). Source: Thermo Fisher Scientific.

Figure 5

Schematic of ions sorted in an ion trap mass spectrometer (ITMS). Ions are accumulated, expelled on demand, and detected.

Figure 6

Schematic of an electrospray ionization (ESI) interface. Charged droplets explode during drying creating charged analytes that are filtered prior to entering a mass analyzer. Additional analyte molecules ionize from collision-induced dissociation (CID) with N₂ molecules.

Figure 7

Schematic of an atmospheric pressure chemical ionization (APCI) interface. Solvent droplets are evaporated prior to the analyte contacting a corona discharge needle. The needle creates primary and secondary ions that transfer charge to analyte molecules during collisions. Additional fragmentation occurs from collision-induced dissociation (CID) with N₂ molecules.

Figure 8

Schematic of a two-dimensional linear ion trap mass spectrometer (2D-ITMS). Ions traverse back and forth along the z-axis, trapped by a radial oscillating electric field (radio frequency). The kinetic energies of the ions are reduced (cooled) by interactions with gas molecules such as helium introduced separately. Ions are radially ejected when the trapping potential is lowered and strike an ion detector. Source: Thermo Fisher Scientific

Figure 9

Schematic of a Penning trap, the central component of a Fourier transform ion cyclotron resonance mass spectrometer (FTMS). Ions enter the box, are trapped in the magnetic field, excited to larger, coherent orbital radii to facilitate detection, and the frequency of current induced in detection plates is measured and transformed to a mass-to-charge ratio.

Figure 10

Schematic of a capillary electrophoresis instrument. Cations, anions and neutral molecules are propelled toward the cathode by electroosmotic flow (EOF) of the buffer. They are separated based on electrophoretic mobility and interaction with the adsorbent before entering a detector positioned at the cathode end of the capillary.