Tien D. Ho

Ionic Liquids in Analytical Chemistry: Fundamentals, Advances, and Perspectives

265 Application of IL-DLLME in the Analysis of Pharmaceutical Entities 265 IL-DLLME in the Analysis of Metal Ions 266 Application of IL-DLLME in the Analysis of Organic Environmental Pollutants 266

Ionic liquids in solid-phase microextraction: A review

Solid-phase microextraction (SPME) has undergone a surge in popularity within the field of analytical chemistry in the past two decades since its introduction. Owing to its nature of extraction, SPME has become widely known as a quick and cost-effective sample preparation technique. Although SPME has demonstrated extraordinary versatility in sampling capabilities, the technique continues to experience a tremendous growth in innovation. Presently, increasing efforts have been directed towards the engineering of novel sorbent material in order to expand the applicability of SPME for a wider range of analytes and matrices. This review highlights the application of ionic liquids (ILs) and polymeric ionic liquids (PILs) as innovative sorbent materials for SPME. Characterized by their unique physico-chemical properties, these compounds can be structurally-designed to selectively extract target analytes based on unique molecular interactions. To examine the advantages of IL and PIL-based sorbent coatings in SPME, the field is reviewed by gathering available experimental data and exploring the sensitivity, linear calibration range, as well as detection limits for a variety of target analytes in the methods that have been developed.

Determination of polychlorinated biphenyls in ocean water and bovine milk using crosslinked polymeric ionic liquid sorbent coatings by solid-phase microextraction.

Crosslinked polymeric ionic liquid (PIL)-based sorbent coatings were employed in the extraction of 21 polychlorinated biphenyls (PCBs) from ocean water and bovine milk using solid-phase microextraction (SPME). The extraction temperature, time, and concentration of sodium chloride added to the matrix were optimized in order to determine the best extraction conditions for the extraction of PCBs. The analytical performance of the crosslinked PIL-based SPME fibers was compared with a commercial 7 µm polydimethylsiloxane (PDMS) fiber using gas chromatography (GC) employing an electron capture detector (ECD) and mass spectrometric detection (MS). Higher sensitivities for PCBs were achieved using PIL-based fibers when compared to PDMS fiber due to the incorporation of benzyl moieties into the PIL structures. The limits of detection (LOD) for all PCBs were determined to be in the low ng L(-1) range using the three studied coatings. Recovery studies were performed for PCBs in ocean water and bovine milk to validate the applicability of the current SPME method.

Selective extraction of genotoxic impurities and structurally alerting compounds using polymeric ionic liquid sorbent coatings in solid-phase microextraction: Alkyl halides and aromatics.

A series of polymeric ionic liquids (PILs) possessing varied chemical makeup and composition were applied as selective solid-phase microextraction (SPME) sorbent coatings for the analysis of genotoxic impurities (GTIs) and related structurally alerting compounds, namely, alkyl halides and aromatics. In addition to exploiting two previously synthesized PILs as selective coatings, two new PILs, namely, N,N-didecyl-N-methyl-D-glucaminium poly(2-methyl-acrylic acid 2-[1-(3-{2-[2-(3-trifluoromethanesulfonylamino-propoxy)-ethoxy]-ethoxy}-propylamino)-vinylamino]-ethyl ester) (poly([DDMGlu][MTFSI])), and poly(1-vinyl-3-propylphenylimidazolium) chloride (poly([VPPIM][Cl])), were designed, synthesized, and their selectivity examined in the extraction of the selected analytes. The glucaminium-based coating was developed to exploit the hydrogen bond-acidic hydroxyl groups within the carbohydrate moiety of the PIL in addition to dispersive capabilities resulting from the cation and anion. The poly([VPPIM][Cl]) coating was tailored to possess π-π interaction capabilities through the phenyl functionality while also containing the hydrogen bond-basic chloride anion. Calibration studies were performed via headspace extraction to determine the sensitivity and limit of detection (LOD) for all analytes with respect to each PIL-based sorbent coating and compared to the polyacrylate (PA) and polydimethylsiloxane (PDMS) sorbent coatings. PILs containing the chloride anion exhibited high selectivity for aniline-based compounds. The glucaminium-based PIL exhibited good sensitivity for larger aliphatic alkyl halides. The poly(1-4-vinylbenzyl-3-hexadecylimidazolium) bis[(trifluoromethyl)sulfonyl] imide (poly([VBHDIM][NTf₂])) PIL coating demonstrated superior selectivity for larger aliphatic/aromatic analytes. The LODs of both commercial and PIL-based coatings for the two classes of GTIs ranged from low part-per-billion (ppb) to mid part-per-trillion (ppt) levels. Recovery studies were performed at two concentration levels within the linear range in order to validate the accuracy of the technique. Scanning electron micrographs were obtained for three PIL-based coatings following approximately 70 extraction/desorption steps, wherein the fiber coatings were observed to be largely smooth and intact.

Polymeric ionic liquid coatings versus commercial solid-phase microextraction coatings for the determination of volatile compounds in cheeses.

The extraction performance of four polymeric ionic liquid (PIL)-based solid-phase microextraction (SPME) coatings has been studied and compared to that of commercial SPME coatings for the extraction of 16 volatile compounds in cheeses. The analytes include 2 free fatty acids, 2 aldehydes, 2 ketones and 10 phenols and were determined by headspace (HS)-SPME coupled to gas chromatography (GC) with flame-ionization detection (FID). The PIL-based coatings produced by UV co-polymerization were more efficient than PIL-based coatings produced by thermal AIBN polymerization. Partition coefficients of analytes between the sample and the coating (Kfs) were estimated for all PIL-based coatings and the commercial SPME fiber showing the best performance among the commercial fibers tested: carboxen-polydimethylsyloxane (CAR-PDMS). For the PIL-based fibers, the highest K(fs) value (1.96 ± 0.03) was obtained for eugenol. The normalized calibration slope, which takes into account the SPME coating thickness, was also used as a simpler approximate tool to compare the nature of the coating within the determinations, with results entirely comparable to those obtained with estimated K(fs) values. The PIL-based materials obtained by UV co-polymerization containing the 1-vinyl-3-hexylimidazolium chloride IL monomer and 1,12-di(3-vinylimiazolium)dodecane dibromide IL crosslinker exhibited the best performance in the extraction of the select analytes from cheeses. Despite a coating thickness of only 7 µm, this copolymeric sorbent coating was capable of quantitating analytes in HS-SPME in a 30 to 2000 µg L(-1) concentration range, with correlation coefficient (R) values higher than 0.9938, inter-day precision values (as relative standard deviation in %) varying from 6.1 to 20%, and detection limits down to 1.6 µg L(-1).

Chemical immobilization of crosslinked polymeric ionic liquids on nitinol wires produces highly robust sorbent coatings for solid-phase microextraction☆

Super elastic nitinol (NiTi) wires were exploited as highly robust supports for three distinct crosslinked polymeric ionic liquid (PIL)-based coatings in solid-phase microextraction (SPME). The oxidation of NiTi wires in a boiling (30%w/w) H2O2 solution and subsequent derivatization in vinyltrimethoxysilane (VTMS) allowed for vinyl moieties to be appended to the surface of the support. UV-initiated on-fiber copolymerization of the vinyl-substituted NiTi support with monocationic ionic liquid (IL) monomers and dicationic IL crosslinkers produced a crosslinked PIL-based network that was covalently attached to the NiTi wire. This alteration alleviated receding of the coating from the support, which was observed for an analogous crosslinked PIL applied on unmodified NiTi wires. A series of demanding extraction conditions, including extreme pH, pre-exposure to pure organic solvents, and high temperatures, were applied to investigate the versatility and robustness of the fibers. Acceptable precision of the model analytes was obtained for all fibers under these conditions. Method validation by examining the relative recovery of a homologous group of phthalate esters (PAEs) was performed in drip-brewed coffee (maintained at 60 °C) by direct immersion SPME. Acceptable recoveries were obtained for most PAEs in the part-per-billion level, even in this exceedingly harsh and complex matrix.

Determination of trace level genotoxic impurities in small molecule drug substances using conventional headspace gas chromatography with contemporary ionic liquid diluents and electron capture detection.

Ionic liquids (ILs) were used as a new class of diluents for the analysis of two classes of genotoxic impurities (GTIs), namely, alkyl/aryl halides and nitro-aromatics, in small molecule drug substances by headspace gas chromatography (HS-GC) coupled with electron capture detection (ECD). This novel approach using ILs as contemporary diluents greatly broadens the applicability of HS-GC for the determination of high boiling (≥ 130°C) analytes including GTIs with limits of detection (LOD) ranging from 5 to 500 parts-per-billion (ppb) of analytes in a drug substance. This represents up to tens of thousands-fold improvement compared to traditional HS-GC diluents such as dimethyl sulfoxide (DMSO) and dimethylacetamide (DMAC). Various ILs were screened to determine their suitability as diluents for the HS-GC/ECD analysis. Increasing the HS oven temperatures resulted in varying responses for alkyl/aryl halides and a significant increase in response for all nitroaromatic GTIs. Linear ranges of up to five orders of magnitude were found for a number of analytes. The technique was validated on two active pharmaceutical ingredients with excellent recovery. This simple and robust methodology offers a key advantage in the ease of method transfer from development laboratories to quality control environments since conventional validated chromatographic data systems and GC instruments can be used. For many analytes, it is a cost effective alternative to more complex trace analytical methodologies like LC/MS and GC/MS, and significantly reduces the training needed for operation.

A chemometric approach toward the detection and quantification of coffee adulteration by solid-phase microextraction using polymeric ionic liquid sorbent coatings.

Solid-phase microextraction (SPME) using cross-linked polymeric ionic liquid (PIL)-based sorbent coatings was used to extract volatile aroma-related compounds from coffee samples. Several PIL-based coatings were screened alongside a commercial poly(acrylate) (PA) SPME coating. The best performing PIL-based SPME fiber, poly(1-vinyl-3-hexadecylimidazolium bis[(trifluoromethyl)sulfonylimide]) with 50% (w/w) 1,12-di(3-vinylbenzylimidazolium)dodecane dibis[(trifluoromethyl)sulfonyl]imide incorporated cross-linker, was used to isolate the volatile fraction of Arabica coffee. To illustrate the importance of trace analyte isolation, a method for the detection and quantification of coffee adulteration is described. Chromatographic profiles obtained by gas chromatography/mass spectrometry (GC/MS) were used to create the chemometric model. Partial least squares (PLS) regression was employed to correlate the aroma-related chemical fingerprint to the degree of adulteration. The proposed method successfully detected fraud down to 1% (w/w) of adulterant and accurately determined the degree of coffee adulteration (i.e, root mean square error of calibration and prediction of 0.54% and 0.83% (w/w), respectively). Finally, important aroma-related compounds including furans, methoxyphenols, pyrazines, and ketones were identified.

Determination of acrylamide in brewed coffee and coffee powder using polymeric ionic liquid-based sorbent coatings in solid-phase microextraction coupled to gas chromatography–mass spectrometry

This study describes a simple and rapid sampling method employing a polymeric ionic liquid (PIL) sorbent coating in direct immersion solid-phase microextraction (SPME) for the trace-level analysis of acrylamide in brewed coffee and coffee powder. The crosslinked PIL sorbent coating demonstrated superior sensitivity in the extraction of acrylamide compared to all commercially available SPME coatings. A spin coating method was developed to evenly distribute the PIL coating on the SPME support and reproducibly produce fibers with a large film thickness. Ninhydrin was employed as a quenching reagent during extraction to inhibit the production of interfering acrylamide. The PIL fiber produced a limit of quantitation for acrylamide of 10μgL(-1) and achieved comparable results to the ISO method in the analysis of six coffee powder samples.

Use of ionic liquids as headspace gas chromatography diluents for the analysis of residual solvents in pharmaceuticals

Graphical abstract Figure. No Caption available. HighlightsTwo ionic liquids (ILs), 1‐butyl‐3‐methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([BMIM][NTf2]) and trihexyltetradecylphosphonium bis[(trifluoromethyl)sulfonyl]imide ([P66614][NTf2]) were examined as contemporary diluents for residual solvent analysis using static headspace gas chromatography (SHS‐GC) coupled with flame ionization detection (FID).A 25‐fold improvement in limit of detection (LD) was observed with respect to traditional HS‐GC diluents, such as N‐methylpyrrolidone (NMP).The established IL‐based method demonstrated LDs ranging from 5.8 parts‐per‐million (ppm) to 20 ppm of residual solvents in drug substances.The analytical performance was demonstrated by determining the repeatability, accuracy, and linearity of the method.Linear ranges of up to two orders of magnitude were obtained for class 3 solvents.Excellent analyte recoveries were obtained in the presence of three different active pharmaceutical ingredients. Abstract In this study, two ionic liquids (ILs), 1‐butyl‐3‐methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([BMIM][NTf2]) and trihexyltetradecylphosphonium bis[(trifluoromethyl)sulfonyl]imide ([P66614][NTf2]) were examined as contemporary diluents for residual solvent analysis using static headspace gas chromatography (SHS‐GC) coupled with flame ionization detection (FID). ILs are a class of non‐molecular solvents featuring negligible vapor pressure and high thermal stabilities. Owing to these favorable properties, ILs have potential to enable superior sensitivity and reduced interference, compared to conventional organic diluents, at high headspace incubation temperatures. By employing the [BMIM][NTf2] IL as a diluent, a 25‐fold improvement in limit of detection (LOD) was observed with respect to traditional HS‐GC diluents, such as N‐methylpyrrolidone (NMP). The established IL‐based method demonstrated LODs ranging from 5.8 parts‐per‐million (ppm) to 20 ppm of residual solvents in drug substances. The optimization of headspace extraction conditions was performed prior to method validation. An incubation temperature of 140 °C and a 15 min incubation time provided the best sensitivity for the analysis. Under optimized experimental conditions, the mass of residual solvents partitioned in the headspace was higher when using [BMIM][NTf2] than NMP as a diluent. The analytical performance was demonstrated by determining the repeatability, accuracy, and linearity of the method. Linear ranges of up to two orders of magnitude were obtained for class 3 solvents. Excellent analyte recoveries were obtained in the presence of three different active pharmaceutical ingredients. Owing to its robustness, high throughput, and superior sensitivity, the HS‐GC IL‐based method can be used as an alternative to existing residual solvent methods.