Research

We are working to develop improve bioanalytical methods by exploiting the properties of Magnetic Ionic Liquids (MILs).

MILs are an intriguing class of ionic liquids comprised of magneto-active anions or cations. MILs exhibit paramagnetic behavior under an applied external magnetic field. By exploiting synthetic chemistry, we have succeeded in developing MILs that exhibit low miscibility in water while also retaining sufficient magnetic susceptibility. Currently, we are interested in developing additional classes of MILs that can be used for the selective extraction of analytes in complex environmental and biological samples.

We are interested in addressing various analytical challenges that are currently facing the pharmaceutical industry. Most recently, we have collaborated extensively with Genentech to develop contemporary and practical analytical methods to quantify genotoxic impurities (GTIs) at trace-level concentrations. GTIs are compounds that can induce genetic mutations, chromosomal breaks, and/or chromosomal rearrangements in humans. Additionally, these compounds can also exhibit potential carcinogenic activity. The United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have imposed stringent regulations on the amount of GTIs present in pharmaceuticals. Depending on the dose and duration of exposure, the allowable daily intake (ADI) can be as low as 1.5 μg/day, which in perspective, would be translated to low parts-per-million (ppm) or sub-ppm concentration ranges of GTIs in drug substances. This highly conservative threshold also applies to pharmaceutical impurities containing structurally alerting functional groups that may possess genotoxic activity. Although GTIs that enter human body may come from drug substances, excipients, degradants, or metabolites, the major source of GTIs is usually active pharmaceutical ingredient (API) manufacturing, which may require the use of genotoxic reagents, solvents, and catalysts. Thus, monitoring the presence of various GTIs in drug substances is of great importance for the pharmaceutical industry.

In a recent collaboration with Genentech, we applied a number of thermally-stable ILs as diluents in the trace-level analysis of two classes of GTIs, namely, alkyl/aryl halides and nitroaromatic compounds, by static headspace gas chromatography coupled to electron capture detection (SHS-GC/ECD). This approach greatly broadens the applicability of SHS-GC for the determination of high boiling GTIs (≥ 130°C) and provides up to a 4000-fold improvement in limits of detection compared to traditional SHS-GC diluents. Optimization of the incubation temperature (up to 210 °C) resulted in varying response for alkyl/aryl halides and enhanced response for nitroaromatic compounds. Excellent recoveries of all GTIs at low ppm-levels were obtained from real APIs.

Solid-phase microextraction (SPME) is a popular sample preparation technique that involves the preconcentration of analytes from a variety of matrices, often without the need for sample pre-treatment. Our group has been focusing on the practical and fundamental aspects of SPME, particularly in the development of highly selective sorbent coatings using polymeric ionic liquids (PILs). The ability to alter the chemical composition of these materials by the means of synthesis or by employing different cation/anion combinations has produced coatings that exhibit superior selectivity for target analyte(s) in various sample matrices.

We have developed an on-fiber UV co-polymerization route to chemically immobilize crosslinked PILs on various SPME supports. The method requires no organic dispersive solvent and is much more rapid compared to traditional SPME fiber preparation methods. Additionally, the crosslinked PIL-based SPME coatings possess excellent thermal and mechanical stability, and are applicable in both headspace and direct-immersion SPME. In one application, polar crosslinked PIL-based SPME coatings were developed for the extraction of polar analytes from complex water samples. Excellent analytical performance and good recovery of these analytes can be obtained using these novel coatings, even after multiple direct-immersion experiments. We are also studying PIL-based bucky gel sorbent coatings in which single-walled carbon nanotubes (CNTs) have been successfully dispersed within the IL prior to free-radical polymerization (see figure below). The high surface area, high mechanical strength, and high thermal stability of CNTs make them particularly attractive when making PIL-hybrid coatings for SPME. Compared to the neat PIL-based sorbent coating, the PIL bucky gel sorbent coatings demonstrated higher extraction efficiency for polycyclic aromatic hydrocarbons. On-going work in our lab is focused on using SPME as a platform to study the way in which molecules interact with carbon nanotubes.

Multidimensional gas chromatography (MDGC) is an extremely valuable tool for the separation, detection, and identification of volatile and semi-volatile constituents in many complex samples. A typical MDGC separation employs two or more gas chromatographic separations in a sequential fashion. In order to achieve a significant improvement in resolution power, the stationary phases employed often possess different selectivities. Until recently, commercial poly(siloxane)- and poly(ethylene glycol)-based stationary phases have been widely applied in MDGC separations. However, their solvation characteristics and thermal stabilities are often limited for particular classes of compounds, such as those complex mixtures often found in the petrochemical industry.

Using the Abraham solvation parameter model as a guiding tool in the structural design of ILs, we have developed low cohesive phosphonium-based IL stationary phases for comprehensive two-dimensional gas chromatography (GC×GC). These new statationary phases were used for the first time as the second dimension column (HP-5 × IL) in the separation of aliphatic hydrocarbons in kerosene. These compounds were the first reported class of ILs that were capable of resolving the aliphatic hydrocarbons (see chromatograms below) while also possessing high thermal stabilities (up to 320°C). On-going studies within the group are focused on understanding the structural attributes of the IL that provide the observed enhanced selectivity and using this knowledge in the development of new classes of stationary phases for applications within the petrochemical, flavors and fragrance, and pharmaceutical industries.