Proton conductivity study on three CS/IL@fle-MOF membranes

The low-cost, high specific surface area and porosity, controlled pore size, and chemical properties of metal–organic framework (MOF) materials have attracted much attention in the exploration of proton conduction. The method of chemically modifying MOF structures or introducing conductive medium into the holes can effectively improve the proton conductivities of the materials. Here, the structural tunability of ionic liquid (IL) and flexible MOF (fle-MOF) materials are matched to give full play to the conductivity of IL, the framework support, and the microporous effect of MOFs, which achieves the synergistic effect of performance and expands the temperature range of proton transfer. Three kinds of CS/IL@fle-MOF membranes were prepared by combining three fle-MOFs with 1-carboxymethyl-3-methylimidazole (CMMIM) in different proportions to obtain 15 pieces of membranes. The comparative analyses show that CS/IL@fle-MOF membranes have excellent proton conduction performance at a wider temperature range (263–353 K) and lower relative humidity (75% RH). Among them, the proton conductivities of CS/CMMIM@MIL-88A-25% and CS/CMMIM@MIL-88B-125% are up to 1.33 and 1.42 S cm⁻¹ at 75% RH and 353 K, respectively; whereas those of CS/CMMIM@MIL-53(Fe)-75% and CS/CMMIM@MIL-88B-125% reach up to 2.1 × 10⁻³ and 1.28 × 10⁻³ S cm⁻¹ at 75% RH and 263 K, respectively. The E_a of CS/CMMIM@fle-MOFs is in the range of 0.1–0.5 eV, suggesting that the proton transport follows predominantly the typical Grotthuss transfer mechanism. The results of this study indicate that the CS/CMMIM@fle-MOF membranes combinations offer great potential for the design of composite porous proton-conducting materials.     

Comparative bioavailability of two zolpidem hemitartrate formulations in healthy human Brazilian volunteers using high-performance liquid chromatography coupled to tandem mass spectrometry

To assess the bioequivalence of two zolpidem hemitartrate formulations in 30 healthy volunteers. Plasma samples were obtained over a 24 h period. Plasma concentrations of zolpidem were analyzed by liquid chromatography coupled to tandem mass spectrometry with positive ion electrospray ionization using multiple reaction monitoring. Values of peak concentration (C_max), area under curve (AUC), half-life, elimination constant, volume of distribution and clearance showed statistically significant differences when comparing women (604.34 ng h/ml, 127.36 ng/ml, 4.4 h, 0.18 1/h, 50.56 L and 8.55 L/h, respectively) and men (276.1 ng h/ml, 70.9 ng/ml, 3.3 h, 0.26 1/h, 91.42 L and 24.34 L/h, respectively), receiving the same dose (5 mg), respectively. The geometric means with corresponding 90% confidence interval for Test/Reference percentage ratios were 99.73% (CI 93.69–106.16) for C_max, 97.44% (90% CI = 91.85–103.37%) for area under curve of plasma concentration until the last concentration observed (AUC_last) and 98.30% (90% CI = 92.48–104.49) for the area under curve between the first sample (pre-dosage) and infinity (AUC_0–inf). Since the 90% CI for AUC_last, AUC_0–inf and C_max ratios were within the 80–125% interval proposed by the US Food and Drug Administration, it was concluded that zolpidem hemitartrate formulation (5 mg orodispersible tablet) is bioequivalent to the zolpidem hemitartrate formulation (Patz SL 5 mg sublingual tablet) with regard to both the rate and the extent of absorption. A new formulation of zolpidem 2.5 mg may be useful in women for the same clinical benefits as the 5 mg formulation in men.     

Volatile organic compounds in head and neck squamous cell carcinoma—An in vitro pilot study

Owing to the lack of specific symptoms, diagnosis of head and neck squamous cell carcinoma (HNSCC) may be delayed. We evaluated volatile organic compounds in tumor samples from patients suffering from HNSCC and tested the hypothesis that there is a characteristic altered composition in the headspace of HNSCC compared with control samples from the same patient with normal squamous epithelium. These results provide the basis for future noninvasive breath analysis in HNSCC. Headspace air of suspected tumor and contralateral control samples in 20 patients were analyzed using ion-mobility spectrometry. Squamous cell carcinoma was diagnosed in 16 patients. In total, we observed 93 different signals in headspace measurements. Squamous cell carcinomas revealed significantly higher levels of volatile cyclohexanol (0.54 ppb_v, 25th to 75th percentiles 0.35–0.86) compared with healthy squamous epithelium (0.24 ppb_v, 25th to 75th percentiles 0.12–0.3; p < 0.001). In conclusion, head and neck squamous cell carcinoma emitted significantly higher levels of volatile cyclohexanol in headspace compared with normal squamous epithelium. These findings form the basis for future breath analysis for diagnosis, therapy control and the follow-up of HNSSC to improve therapy and aftercare.     

A novel LC–MS/MS method for the determination of ziritaxestat in rat plasma and its pharmacokinetic study

Ziritaxestat is a first-in-class autotoxin inhibitor. The purpose of this study was to develop a liquid chromatography/electrospray ionization tandem mass spectrometric (LC–MS/MS) method for the determination of ziritaxestat in rat plasma. The plasma sample was deproteinated using acetonitrile and then separated on an Acquity BEH C₁₈ column with water containing 0.1% formic acid and acetonitrile as mobile phase, which was delivered at 0.4 ml/min. Ziritaxestat and the internal standard (crizotinib) were quantitatively monitored with precursor-to-product transitions of m/z 589.3 > 262.2 and m/z 450.1 > 260.2, respectively. The total running time was 2.5 min. The method showed excellent linearity over the concentration range 0.5–2000 ng/ml, with correlation coefficient >0.9987. The extraction recovery was >82.09% and the matrix effect was not significant. Inter- and intra-day precisions (RSD) were <11.20% and accuracies were in the range of −8.50–7.45%. Ziritaxestat was demonstrated to be stable in rat plasma under the tested conditions. The validated LC–MS/MS method was successfully applied to study the pharmacokinetic profiles of ziritaxestat in rat plasma after intravenous and oral administration. Pharmacokinetic results demonstrated that ziritaxestat displayed a short half-life (~3 h) and low bioavailability (20.52%).     

Assessment of synthetic cannabinoid FUB-AMB and its ester hydrolysis metabolite in human liver microsomes and human blood samples using UHPLC–MS/MS

FUB-AMB, an indazole carboxamide synthetic cannabinoid recreational drug, was one of the compounds most frequently reported to governmental agencies worldwide between 2016 and 2019. It has been implicated in intoxications and fatalities, posing a risk to public health. In the current study, FUB-AMB was incubated with human liver microsomes (HLM) to assess its metabolic fate and stability and to determine if its major ester hydrolysis metabolite (M1) was present in 12 authentic forensic human blood samples from driving under the influence of drug cases and postmortem investigations using UHPLC–MS/MS. FUB-AMB was rapidly metabolized in HLM, generating M1 that was stable through a 120-min incubation period, a finding that indicates a potential long detection window in human biological samples. M1 was identified in all blood samples, and no parent drug was detected. The authors propose that M1 is a reliable marker for inclusion in laboratory blood screens for FUB-AMB; this metabolite may be pharmacologically active like its precursor FUB-AMB. M1 frequently appears in samples in which the parent drug is undetectable and can point to the causative agent. The results suggest that it is imperative that synthetic cannabinoid laboratory assay panels include metabolites, especially known or potential pharmacologically active metabolites, particularly for compounds with short half-lives.     

Capillary electrophoresis and ultra-high-performance liquid chromatography methods in clinical monitoring of creatinine in human urine: A comparative study

Creatinine is an important diagnostic marker and is also used as a standardization tool for the quantitative evaluation of exogenous/endogenous substances in urine. This study aimed at evaluating and comparing three analytical approaches, based on hyphenations of different separation [two-dimensional capillary isotachophoresis (CITP–CITP), capillary zone electrophoresis (CZE), ultra-high-performance liquid chromatography (UHPLC)] and detection [conductivity (CD), ultraviolet (UV), tandem mass spectrometry (MS/MS)] techniques, for their ability to provide reliable clinical data along with their suitability for the routine clinical use (cost, simplicity, sample throughput). The developed UHPLC–MS/MS, CITP–CITP–CD, and CZE–UV methods were characterized by favorable performance parameters, such as linearity (r ˃ 0.99), precision (relative standard deviation, 0.22–2.97% for the creatinine position in analytical profiles), and recovery (87.1–115.1%). Clinical data, obtained from the analysis of 24 human urine samples by a reference enzymatic method, were comparable with those obtained by the tested methods (Passing–Bablok regression and Bland–Altman analysis), approving their usefulness for the routine clinical use. In this context, the UHPLC–MS/MS method provides benefits of enhanced orthogonality/accuracy and high sample throughput (threefold shorter total analysis times than the CE methods), whereas advantages of the CE methods for routine labs are simplicity and low cost of both the instrumentation and measurements.     

Accurate,sensitive determination of omega-6 and omega-3 polyunsaturated fatty acids in human plasma,urine samples

Quantitative determination of omega-6 and omega-3 polyunsaturated fatty acids in human plasma and urine with high accuracy and precision provides significant information to monitor the underlying etiology of several diseases. In this regard, liquid chromatography-mass spectrometry is a good choice owing to its great selectivity and sensitivity. Additionally, the hybrid quadrupole–time of flight–mass spectrometer systems provides easy identification of target compounds with superior mass measurements. In this study, an analytical method has been developed for simple, accurate and simultaneous determination of linoleic acid, arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid in a short chromatographic analysis period. The developed method is suitable for the quantitative detection of these four compounds with detection limits ranging between 1.1–3.0 ng ml⁻¹ and its applicability was assessed in human urine and plasma samples. As a result, acceptable accuracy (between 83 and 111%) and good precision (<6%) were obtained for target compounds using matrix matching calibration strategy.     

Identification of metabolic markers in patients with type 2 Diabetes by Ultrafast gas chromatography coupled to electronic nose. A pilot study

Metabolomics is a potential tool for the discovery of new biomarkers in the early diagnosis of diseases. An ultra-fast gas chromatography system equipped to an electronic nose detector (FGC eNose) was used to identify the metabolomic profile of Volatile Organic Compounds (VOCs) in type 2 diabetes (T2D) urine from Mexican population. A cross-sectional, comparative, and clinical study with translational approach was performed. We recruited twenty T2D patients and twenty-one healthy subjects. Urine samples were taken and analyzed by FGC eNose. Eighty-eight compounds were identified through Kovats's indexes. A natural variation of 30% between the metabolites, expressed by study groups, was observed in Principal Component 1 and 2 with a significant difference (p < 0.001). The model, performed through a Canonical Analysis of Principal coordinated (CAP), allowed a correct classification of 84.6% between healthy and T2D patients, with a 15.4% error. The metabolites 2-propenal, 2-propanol, butane- 2,3-dione and 2-methylpropanal, were increased in patients with T2D, and they were strongly correlated with discrimination between clinically healthy people and T2D patients. This study identified metabolites in urine through FGC eNose that can be used as biomarkers in the identification of T2D patients. However, more studies are needed for its implementation in clinical practice.     

Mechanistic Study of the Solvent-Dependent Formation of Extended and Stacked Supramolecular Polymers Composed of Bis(imidazolylporphyrinatozinc) Molecules

Bis(imidazolylporphyrinatozinc) molecules linked through a 1,3-butadiynylene moiety respond to the solvents they are dissolved in to afford exclusively extended (E) or stacked (S) supramolecular polymers. This system is expected to be a solvation/desolvation indicator. However, the principles underlying the solvent-dependent formation of the two types of polymers and the mechanism of the transformation between them are unclear. The formation of the polymers is considered to depend on the two types of complementary coordination bonds that can be formed and the π–π interactions between the porphyrins. In this study, the contributions and solvent dependence of both the coordination bonds and the π–π interactions have been investigated. The results clearly indicate that the coordination bonds are weakly or little solvent-dependent, and that the π–π interactions function effectively only in the inner porphyrins of the S-polymer and are strongly solvent-dependent. Thermodynamic analysis revealed that the formation of the E- or S-polymer in solution is determined by the total energies and the type of solvent used. The transformation of the E- to S-polymer was investigated by gel permeation chromatography. The kinetics of the transformation were also determined. The role of the terminal imidazolylporphyrinatozinc moieties was also investigated: The results indicate that the transformation from the E- to S-polymer occurs by an exchange mechanism between the polymers, induced by attack of terminal free imidazolyl groups on a polymer to zinc porphyrins on other polymers.     

FeOOH@Metal–Organic Framework Core–Satellite Nanocomposites for the Serum Metabolic Fingerprinting of Gynecological Cancers

High-throughput metabolic analysis is of significance in diagnostics, while tedious sample pretreatment has largely hindered its clinic application. Herein, we designed FeOOH@ZIF-8 composites with enhanced ionization efficiency and size-exclusion effect for laser desorption/ionization mass spectrometry (LDI-MS)-based metabolic diagnosis of gynecological cancers. The FeOOH@ZIF-8-assisted LDI-MS achieved rapid, sensitive, and selective metabolic fingerprints of the native serum without any enrichment or purification. Further analysis of extracted serum metabolic fingerprints successfully discriminated patients with gynecological cancers (GCs) from healthy controls and also differentiated three major subtypes of GCs. Given the low cost, high-throughput, and easy operation, our approach brings a new dimension to disease analysis and classification.