Combining Two Selection Principles: Sensor Arrays Based on Both Biomimetic Recognition and Chemometrics

Electronic noses mimic smell and taste senses by using sensor arrays to assess complex samples and to simultaneously detect multiple analytes. In most cases, the sensors forming such arrays are not highly selective. Selectivity is attained by pattern recognition/chemometric data treatment of the response pattern. However, especially when aiming at quantifying analytes rather than qualitatively detecting them, it makes sense to implement chemical recognition via receptor layers, leading to increased selectivity of individual sensors. This review focuses on existing sensor arrays developed based on biomimetic approaches to maximize chemical selectivity. Such sensor arrays for instance use molecularly imprint polymers (MIPs) in both e-noses and e-tongues, for example, to characterize headspace gas compositions or to detect protein profiles. Other array types employ entire cells, proteins, and peptides, as well as aptamers, respectively, in multisensor systems. There are two main reasons for combining chemoselectivity and chemometrics: First, this combined approach increases the analytical quality of quantitative data. Second, the approach helps in gaining a deeper understanding of the olfactory processes in nature

Development and validation of a fast ionic liquid-based dispersive liquid-liquid microextraction procedure combined with LC-MS/MS analysis for the quantification of benzodiazepines and benzodiazepine-like hypnotics in whole blood

To date, thorough clean-up of complex biological samples remains an essential part of the analytical process. The solid phase extraction (SPE) technique is the well-known standard, however, its main weaknesses are the labor-intensive and time-consuming protocols. In this respect, dispersive liquid-liquid microextractions (DLLME) seem to offer less complex and more efficient extraction procedures. Furthermore, ionic liquids (ILs) - liquid salts - are emerging as new promising extraction solvents, thanks to their non-flammable nature, negligible vapor pressure and easily adaptable physiochemical properties. In this study, we investigated whether ILs can be used as an extraction solvent in a DLLME procedure for the extraction of a broad range of benzodiazepines and benzodiazepine-like hypnotics in whole blood samples. 1.0mL whole blood was extracted using an optimized 30-min IL-based DLLME procedure, followed by LC-ESI(+)-MS/MS analysis in scheduled MRM scan mode. The optimized analytical method was successfully validated for 7-aminoflunitrazepam, alprazolam, bromazepam, clobazam, clonazepam, clotiazepam, diazepam, estazolam, ethyl loflazepate, etizolam, flurazepam, lormetazepam, midazolam, oxazepam, prazepam, temazepam, triazolam, zolpidem and zopiclone. The method showed good selectivity for endogenous interferences based on 12 sources of blank whole blood. No benzodiazepine interferences were observed, except for clorazepate and nordiazepam, which were excluded from the quantitative method. Matrix-matched calibration curves were constructed covering the whole therapeutic range, including low toxic plasma concentrations. Accuracy and precision results met the proposed acceptance criteria for the vast majority of compounds, except for brotizolam, chlordiazepoxide, cloxazolam, flunitrazepam, loprazolam, lorazepam and nitrazepam, which can only be determined in a semi-quantitative way. Recoveries were within the range of 24.7%-127.2% and matrix effects were within 20.0%-92.6%. Both parameters were tested using 5 sources of whole blood and coefficients of variance were below 20%. Overall, the applicability of ILs as promising solvents for the extraction of benzodiazepines in whole blood samples has been proven. Moreover, a fast and easy IL-based DLLME procedure was developed for the quantification of 19 benzodiazepines and benzodiazepine-like hypnotics.</p

Fast and easy extraction of antidepressants from whole blood using ionic liquids as extraction solvent

This study aims to prove that ionic liquids (ILs) can be used as extraction solvents in a liquid-liquid microextraction, coupled to LC-MS/MS, for the quantification of a large group of antidepressants in whole blood samples. The sample preparation procedure consisted of adding 1.0mL aqueous buffer pH 3.0 and 60µL of IL (1-butyl-3-methylimidazolium hexafluorophosphate) to 1.0mL whole blood. Subsequently, a 5-min rotary mixing step was performed followed by centrifugation. The lower IL phase was collected, diluted 1:10 in methanol and 10µL was injected into the LC-MS/MS. The following analytes were included in the full-quantitative method: agomelatine, amitriptyline, bupropion, clomipramine, dosulepin, doxepin, duloxetine, escitalopram, fluoxetine, imipramine, maprotiline, mianserin, mirtazapine, nortriptyline, paroxetine, reboxetine, trazodone and venlafaxine. Selectivity was checked for 10 different whole blood matrices. Additionally, possible interferences of deuterated standards or other antidepressants were evaluated. Overall, no interferences were found. For each analyte a matrix-matched calibration curve was constructed (7 levels, n = 6), covering therapeutic and low toxic concentrations. Accuracy and precision were evaluated over eight days, at three concentration levels (n = 2). Bias, repeatability and intermediate precision results met with the proposed validation criteria, except for fluvoxamine, which was therefore only included in the semi-quantitative method. LOQs were set at the lowest calibrator concentration and LOD values were - for most analytes - within a range of 1-2ng/mL. Recoveries (RE) and matrix effects (ME) were evaluated for five types of donor whole blood, at two concentration levels. RE values were within a range of 53.11-132.98%. ME values were within a range of 61.92-123.24%. In conclusion, this study proves the applicability of ILs as extraction solvents for a large group of antidepressants in complex whole blood matrices.</p

Evaluation of the suitability of ionic liquid-based liquid-liquid microextractions for blood protein removal

The analysis of biological samples, such as whole blood, comes with several sample preparation challenges. Biological matrices often contain a variety of endogenous components that can interfere with the determination of xenobiotics. Especially blood plasma proteins (e.g. serum albumin) are known to interfere with electrospray ionization and result in analyte ion suppression. Sample preparation techniques should guarantee adequate removal of these biomolecules. The current study aims to determine to which extent proteins are removed from whole blood samples, using ionic liquid-based dispersive liquid-liquid microextraction (IL-DLLME). A qualitative comparison of the protein presence in extracts of IL-DLLME, solid-phase extraction (SPE) and protein precipitation (PP) was performed, using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Additionally, UV/VIS spectrophotometry was used to determine the protein content of a whole blood sample and IL-DLLME, SPE and PP extracts of the same sample. Finally, a quantitative comparison of matrix effects of benzodiazepines present in both whole blood and water samples. SDS-PAGE results showed that IL-DLLME extracts still contained proteins (i.e. albumin, hemoglobin); however, band intensities were comparable to SPE extracts. Spectrophotometric tests showed a total protein content of approximately 2 mg/mL in the final extracts. PP showed the highest protein extraction rate (19 mg/mL). Quantitative ME results showed no significant differences (α = 0.05) between blood and water IL-DLLME extracts. Overall, this is the first study to conclude that IL-DLLME is able to sufficiently remove blood proteins from whole blood samples, in order to avoid significant ion suppression.</p

Medical Findings and Toxicological Analysis in Infant Death by Balloon Gas Asphyxia:A Case Report

In recent years, the increasing number of asphyxiation cases due to helium inhalation is remarkable. All described cases in the literature where diagnosed as suicide. In this article, however, we describe a triple infant homicide in which helium, as balloon gas, was administered to three young children after sedation causing asphyxiation and death through the medical findings and toxicological analysis. During autopsy, in addition to standard toxicological samples, gas samples from lungs as well as lung tissue itself were directly collected into headspace vials. Besides routine toxicological analysis, which revealed toxic levels of doxylamine, qualitative analysis on gas and lung samples was performed using headspace gas chromatography-mass spectrometry. As carrier gas, the commonly used helium was replaced by nitrogen. In gas samples from lungs of all three children, no helium was found. Nevertheless, lung tissue samples were found positive on helium. Therefore, sedation followed by asphyxia due to helium inhalation can strongly be assumed as the cause of death of all three children.</p

Vein graft surveillance: Is graft revision without angiography justified and what criteria should be used?

AbstractPurpose: The objective of this study was to assess the accuracy of color-flow duplex surveillance parameters to detect infrainguinal vein graft stenoses and to investigate whether graft revision without angiography is justified. Methods: In a prospective study in which three centers participated, the data of graft surveillance in 300 patients were analyzed. For the evaluation of surveillance criteria all patients underwent a digital subtraction angiography if a graft stenosis was suspected. To create a control group, in patients with normal grafts a consented digital subtraction angiography was performed also. From these data the accuracy of seven duplex and three ankle blood pressure-derived variables was assessed. The relation between various surveillance criteria and continued graft patency was determined with life table analysis with the transient state method. Results: The mean follow-up period was 20 months (range, 1 to 40 months). At univariate and multivariate analysis the peak systolic velocity (PSV) ratio provided the best correlation with angiographic stenoses ≥70% (PSV ratio cutoff 3.0: sensitivity 80%, specificity 84%). This finding did not differ between the participating centers. With life table methods it was demonstrated that the best combination of efficacy (limitation of the number of unnecessary revisions), safety (minimal number of correctable lesions missed), and reduction of angiograms was obtained by a two-parameter surveillance algorithm. This algorithm included a PSV ratio <2.5 to delineate patients in whom a conservative approach without angiography or revision was appropriate, a PSV ratio ≥4.0 to indicate patients in whom vein graft revision without angiography could be scheduled, and a group with PSV ratios between 2.5 and 4.0 in whom angiography was to be performed to determine clinical management on the basis of the stenosis severity. This algorithm had a positive predictive value of 93% and a negative predictive value of 89%. In addition, it resulted in a reduction of the number of angiograms of 49% compared with a policy of angiographies in all patients with a PSV ratio ≥2.5. Conclusions: The best criterion to identify a failing graft is the PSV ratio. With a two-parameter algorithm for vein graft surveillance, the incidence of unnecessary revisions and of missed high-grade lesions was acceptably low, whereas the number of angiograms was reduced by one half. (J Vasc Surg 1998;27:399-413.