Chiral zeolite beta used as stationary phase for enantioseparation in miniaturized open tubular capillary electrochromatography with amperometric detection.

BACKGROUND: With the rapid growth of the demand for optically pure compounds in the fields of biology, medicine and stereospecific synthesis, it is of great importance to develop efficient, economical, simple enantioseparation and analysis methods. Open tubular capillary electrochromatography (OT-CEC) has attracted much attention in the field of chiral separation, but its column capacity and the sensitivity of common-used optical detection are relatively low. Zeolite beta nanomaterial is both enantioselective and size-selective, providing suitable chiral microenvironment for chiral recognition, and amperometric detection (AD) avoids the low sensitivity caused by the short optical path in optical detection to some extent. RESULTS: Zeolite beta nanomaterials with different particle sizes (25, 50 and 200 nm) were synthesized, and the morphology and structure were characterized by scanning electron microscopy and X-ray diffraction. Then, a novel chiral OT column was prepared by one-step method using zeolite beta nanomaterial as chiral stationary phase, and its separation performance was characterized by miniaturized CEC with AD (mini-CEC-AD) device. Under the optimum conditions, six groups of chiral drugs achieved baseline separation. Norepinephrine enantiomers were used for evaluating the inter-day, intra-day and inter-column reproducibility of the prepared open-tubular column. The relative standard deviations of migration time, peak area, resolution and selectivity factor were within 8.7 %. The limits of detection for norepinephrine enantiomers were 0.18 µg mL-1 (S/N = 3), and the average recoveries were in range of 96.7-105.0 %. This developed method has been successfully applied to the analysis of impurity enantiomer in potassium dichromate (+)-norepinephrine injection sample. SIGNIFICANCE: Zeolite beta nanomaterial was used as the stationary phase to prepare chiral OT columns for the first time, and this one-step preparation method is simple and easy. The introduction of zeolite beta enriches the types of chiral stationary phase materials in electrochromatographic columns, and mini-OT-CEC-AD system provides an alternative for fast enantioseparation of chiral compounds.

Deep eutectic solvents combined with beta-cyclodextrin derivatives for chiral separation of typical adrenergic receptor agonists by capillary electrophoresis with amperometric detection.

Enantioseparation has always been one of the research hotspots and difficulties in the field of modern separation science. In this work, a binary chiral electrophoretic separation system was constructed using deep eutectic solvents (DESs) coupled with beta-cyclodextrin derivatives based on capillary electrophoresis with amperometric detection system, and five groups of typical adrenergic receptor agonists (adrenaline, salbutamol, isoproterenol, norepinephrine and terbutaline) were selected as the model enantiomers. The effects of additive types and contents of DESs and cyclodextrins, and the pH value and concentration of the running buffer on the resolution of the selected chiral compounds were investigated in detail. The mechanism of DESs improving separation was explored preliminarily by means of UV spectrophotometry, which was further verified based on the comparison of single and mixed components of choline chlorine-urea DES. Under the optimum conditions, the relative standard deviations for inter-day and intra-day repeatability of the migration time, peak area and resolution for adrenaline and salbutamol were within 8.7%, and the limits of detection reached 0.030 µg mL-1 (S/N = 3). The recovery data were in the range of 96.3-118.7%. The developed methods have been applied for the analyses of (+)-adrenaline hydrochloride injection and (±)-salbutamol aerosol. This binary chiral electrophoretic separation system by CE-AD has high detection sensitivity and low analytical cost, providing an alternative for the separation and analysis of chiral drugs.

Evaluation of homochiral zeolitic imidazolate framework-8 supported open-tubular column by miniaturized capillary electrochromatography with amperometric detection.

A novel kind of chiral open-tubular (OT) column was established with homochiral zeolitic imidazolate framework-8 nanomaterials using L-histidine as the chiral carbon center (L-His-ZIF-8). The morphologies of L-His-ZIF-8 nanoparticles and chiral OT column were characterized by scanning electron microscopy. The effects of L-His-ZIF-8 concentrations, pH values, and concentrations of the running buffer on the resolution of the selected chiral compounds were investigated based on miniaturized capillary electrochromatography with amperometric detection system (mini-CEC-AD), respectively. The separation performances of the prepared L-His-ZIF-8@OT chiral columns were explored under the optimal conditions, and the RSDs of run-to-run, day-to-day, and column-to-column reproducibility were less than 6.7% using salbutamol raceme as the model enantiomers. The prepared chiral OT columns have been successfully applied to the enantioseparation of one pair of amino acid enantiomers, two pairs of racemic drugs, and three pairs of neurotransmitter enantiomers. Under the optimum conditions, the prepared OT columns were applied to real-world sample analysis of salbutamol aerosol. The limits of detection of salbutamol raceme were 0.90 µg·mL-1 (S/N = 3), and the recovery was 80.4-82.7%. The assay results indicated that this kind of chiral OT column modified with homochiral L-His-ZIF-8 possesses good reproducibility and stability. This developed mini-OT-CEC-AD system has some attractive characteristics of sensitivity and low cost, providing a potential way for the separation of chiral compounds.

Preparation and evaluation of chiral open-tubular columns supported with zeolite silica nanoparticles and single/dual chiral selectors using capillary electrochromatography with amperometric detection.

In this work, novel stationary phase coatings by zeolite SiO2NPs coupled with ß-cyclodextrin (ß-CD) or ß-CD/L-phenylalanine were developed for chiral open-tubular capillary electrochromatography (OT-CEC). The OT columns were prepared taking advantage of the strong adhesion of polydopamine in one-step method. Scanning electron micrography and electroosmotic flow were used to characterize the prepared single/dual-selector OT columns. Chiral separation of four chiral analytes (catechin/epicatechin, ephedrine/pseudoephedrine, ritodrine and salbutamol) was carried out in order to evaluate the performance of the prepared columns in OT-CEC with amperometric detection system. In terms of migration time, peak area, resolution, and selectivity factor of catechin/epicatechin and salbutamol, the run-to-run, day-to-day, and column-to-column repeatability were within 8.9%. Under the optimum conditions, the developed methods were applied for the analyses of Chinese herbal medicine Catechu herbs and salbutamol aerosol samples.

Tween 20-capped gold nanoparticles for selective extraction of free low-molecular-weight thiols in saliva followed by capillary electrophoresis with contactless conductivity detection.

Low-molecular-weight thiols are widely present in human fluids, and are regarded as a kind of potential broad-spectrum evaluation indicators for some clinical diseases. In this work, gold nanoparticles capped with Tween 20 were used for purification and microextraction of the main free thiols (cysteine, homocysteine, glutathione and methionine) in saliva based on Au-S bond formation. Ultrasound further sped up the releasing of the target analytes, and the releasing time needed was only 10 min, and the required sample volume was only 40 µL. The desorption solution could be directly injected for electrophoretic analysis without derivatization, and field-amplified sample stacking of electrophoretic online enrichment technology further improved the detection sensitivity. The synergistic enrichment effect made the enrichment factors of four analytes reach 1119-2067 times. This developed method was applied for the analyses of saliva samples of healthy volunteers. Acceptable sensitivity (LODs: 0.15-1.5 ng mL-1) and recoveries (97.6-116%) were obtained in the saliva sample matrix. This proposed method provides an alternative for the sensitive detection of low-molecular-weight thiols in noninvasive body fluids, which has potential application prospect in the preliminary noninvasive diagnosis of diabetes, cardiovascular diseases, etc.

Rapid preparation and evaluation of chiral open-tubular columns supported with bovine serum album and zeolite imidazolate framework-8 for mini-capillary electrochromatography.

In this work, a class of novel and eco-friendly open-tubular (OT) chiral column was presented for the first time by one step preparation with zeolite imidazolate framework-8 (ZIF-8) and bovine serum album (BSA) based on electrostatic adsorption and adsorption affinity. This stationary phase materials combined the features of large surface areas and adsorption affinity of ZIF-8, and also the multiple chiral binding sites of BSA, which contributes to the π-interaction and hydrophobic interaction with the analytes. The separation performance of BSA@ZIF-8-OT chiral columns was evaluated with a miniaturized capillary electrochromatography and amperometric detection (mini-CEC-AD) system; in particular, nine groups of model molecules, including homologues, structural isomers, and chiral compounds, were baseline separated under the certain optimum conditions. The RSDs of run-to-run, day-to-day, column-to-column, and batch-to-batch reproducibility were less than 13.8 %. Furthermore, the prepared OT columns were successfully applied to fast analysis of ephedrine isomers in Chinese herb ephedra, and the LODs achieved 1.5-2.0 ng mL-1 (S/N=3) by an electrophoretic stacking technique of moving chemical reaction boundary. This mini-CEC-AD system with BSA@ZIF-8-OT chiral columns provides a promising potential in pharmaceutical analysis due to its fast, sensitive, enantioselective, and low-cost characteristics.

Zeolitic imidazolate framework-8 reinforced hollow-fiber liquid-phase microextraction of free urinary biomarkers of whole grain intake followed by CE analysis.

The whole grain intake is closely associated with human health. In this work, three-phase dynamic hollow-fiber liquid-phase microextraction reinforced with 0.10 mg/mL 30 nm zeolitic imidazolate framework-8 nanoparticles was introduced for purification and enrichment of free urinary metabolite biomarkers of whole grain intake. Eight milliliters of HCl (pH 3.00) and 8 µL of 300 mM NaOH solutions were used as the donor and acceptor phases, respectively. The temperature and stirring rate were kept at 25℃ and 500 rpm, and the extraction time was 40 min. The extraction process required no further desorption, and the resultant extract was directly used for electrophoretic analysis without derivatization. Based on the synergistic effect of hollow-fiber liquid-phase microextraction and the electrophoretic stacking, the enrichment factors of 3,5-dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-1-propionic acid reached 1018-1034 times, and their limits of detection achieved 0.33-0.67 ng/mL (S/N = 3) in urine matrix. The developed method has been successfully used for urine analysis, and the sample recovery data were in the range of 97.0-103.5%. This developed method provided an attractive alternative for the determination of urinary metabolite biomarkers of whole grain intake due to its sensitive, fast, low-cost, and environmental-friendly features.

ß-cyclodextrin modified quantum dots as pseudo-stationary phase for direct enantioseparation based on capillary electrophoresis with laser-induced fluorescence detection.

In recent years, quantum dots (QDs) have attracted a tremendous amount of attention due to their compelling features. In this work, a kind of composite QDs based on ß-cyclodextrin (ß-CD) and its derivatives modification was prepared, and for the first time utilized to separate and determine enantiomers in the combined system of capillary electrophoresis with laser-induced fluorescence detection (CE-LIF). By taking advantages of the inclusion complexation of ß-CD and the fluorescence property of QD core, the composite QDs were added into the running buffer as pseudo-stationary phase. The resultant CE-LIF method accomplished enantioseparation for six groups of model analytes without need of capillary preparation and analyte derivatization. The effects of composite QDs concentration, the pH value and concentration of the running buffer on resolution have been investigated individually. The RSDs of interday and intraday repeatability were in the range of 2.7-8.1%, 0.7-3.9%, and 1.5-3.8% for the peak area, migration time and resolution, respectively. The theoretical calculation results of the binding energies and binding constant further validated the interaction mechanism of composite QDs and target analytes. Furthermore, this developed method was successfully applied to the analysis of the active components (catechin and epicatechin) in Chinese herb Catechu, and the recoveries were in the range of 92.2-108%. The experimental results suggested that the preparation strategy of the composite QDs is appropriate for enantioseparation of more enantiomers by adjusting the modifiers on the surface of QDs, which is particularly promising for electrophoretic enantioseparation based on fluorescence detection, especially for those analytes lacking proper derivative functional groups.

Double surfactants-assisted electromembrane extraction of cyromazine and melamine in surface water, soil and cucumber samples followed by capillary electrophoresis with contactless conductivity detection.

BACKGROUND: Cyromazine (CYR) and its main degradation product melamine (MEL) are attracting wide attention due to their potential hazards to the environment and humans. In this work, double surfactants-assisted electromembrane extraction (DS-EME) by Tween 20 and alkylated phosphate was firstly used for purification and extraction of CYR and MEL, and the extract was directly analyzed by capillary electrophoresis with capacitively coupled contactless conductivity detection. RESULTS: Under the optimum conditions, two targets could be well separated from the main interferences, including common biogenic amines and inorganic cations within 14 min. This developed method was successfully applied to the analyses of surface water, soil and cucumber samples, and the average recoveries were in the range 93.3-112%. DS-EME provided a synergistic purification and enrichment effect for CYR and MEL by adding Tween 20 and alkylated phosphate into donor phase and supporting liquid membrane, respectively. Satisfactory limits of detection [0.2-1.5 ng mL-1 , signal-to-noise ratio (S/N) = 3] could be obtained in the tested sample matrices, and the corresponding enrichment factors were up to 115∼123 times. CONCLUSION: This developed method provides an alternative for the simultaneous analysis of CYR and MEL in complex real-world samples. © 2019 Society of Chemical Industry.

Salt-effect enhanced hollow-fiber liquid-phase microextraction of glutathione in human saliva followed by miniaturized capillary electrophoresis with amperometric detection.

A hollow-fiber liquid-phase microextraction (HF-LPME) method was established for purification and enrichment of glutathione (GSH) in human saliva followed by a miniaturized capillary electrophoresis with amperometric detection system (mini-CE-AD). Based on regulating isoelectric point and increasing salt effect to modify donor phase, HF-LPME could provide high enrichment efficiency for GSH up to 471 times, and the extract was directly injected for mini-CE-AD analysis. The salt-effect enhanced HF-LPME/mini-CE-AD method has been successfully applied to saliva analysis, and acceptable LOD (0.46 ng/mL, S/N = 3) and recoveries (92.7-101.3%) could be obtained in saliva matrix. The sample pretreatment of this developed method was simple and required no derivatization, providing a potential alternative for non-invasive fluid analysis using portable instrument.

Electrophoretic analysis of polyamines in exhaled breath condensate based on gold-nanoparticles microextraction coupled with field-amplified sample stacking.

In this work, citrate-capped gold-nanoparticles (citrate-AuNPs) have been firstly used for selective extraction of trace polyamines, putrescine (Put) and cadaverine (Cad), followed by field-amplified sample stacking (FASS) coupled with capillary electrophoresis and capacitively coupled contactless conductivity detection (FASS-CE-C4D). Put and Cad were extracted by electrostatic attractions between the amine group of the polyamines and the citrate ligands adsorbed on the surfaces of AuNPs. AuNPs microextraction (AuNPs-ME) effectively shortened preparation time (50 min) by introducing ultrasound, and the required sample extraction volume was only 1 mL. Furthermore, a synergistic enrichment strategy based on off-line AuNPs-ME and on-line FASS significantly improved the detection sensitivity, making the enrichment factors up to 1726-1887 times. Under the optimum conditions, Put and Cad could be well separated from the potential coexisting substances and then directly determined by CE-C4D without derivatization. Due to its low sample consumption, high sensitivity (LODs: 0.070-0.17 ng mL-1), and acceptable recoveries (90-105%), this AuNPs-ME/FASS-CE-C4D method provides a rapid, economical and eco-friendly approach for direct determination of polyamines in human exhaled breath condensate, and has potential application prospects in preliminary noninvasive diagnosis of oral and respiratory inflammation.

Sensitive determination of aldehyde metabolites in exhaled breath condensate using capillary electrophoresis with laser-induced fluorescence detection.

A novel capillary electrophoresis with laser-induced fluorescence detection method has been developed for the analysis of aldehyde metabolism biomarkers for oxidative stress in exhaled breath condensate (EBC), and fluorescein 5-thiosemicarbazide was used as a derivatization reagent. In a simple capillary zone electrophoresis mode, ten low molecular weight aldehydes (LMWAs) could be well separated within 30 min. The reaction efficiency was doubled by increasing sample solution pH and magnetic stirring, and the LODs of this method reached 0.16-3.4 nM (S/N = 3). Acceptable recoveries (82.1-115%) were obtained for EBC samples, and the RSD data were within 7.9%. This developed method has been applied for the analyses of EBC samples and evaluation of the correlation between smoking and the contents of aldehyde metabolites in EBC. Due to no need of buffer additives and sample preconcentration, this proposed method may provide an appealing alternative for the trace analyses of LMWAs in noninvasive biofluids. Graphical abstract ᅟ.

Tributyl phosphate assisted hollow-fiber liquid-phase microextraction of short-chain fatty acids in microbial degradation fluid using capillary electrophoresis-contactless coupled conductivity detection.

A tributyl phosphate assisted hollow-fiber liquid-phase microextraction coupled with capillary electrophoresis-contactless coupled conductivity detection (HF-LPME/CE-C4D) method has been developed for trace analysis of common short-chain fatty acids (SCFAs) without derivatization. Under the optimum conditions, ten SCFAs including a pair of isomers were well separated from their homologous FAs and the main coexisting inorganic anions within 40 min. Tributyl phosphate assisted HF-LPME produced excellent purification and enrichment for the model sample with high-salt matrix, microbial degradation fluid, and the limits of detection could reach 0.072-0.67 ng/mL (S/N = 3). Owing to its high sensitivity, good linearity, and acceptable recovery, this proposed method provided a sensitive and environment-friendly alternative for trace analysis of SCFAs in complicated samples.

Electromembrane extraction of diamine plastic restricted substances in soft drinks followed by capillary electrophoresis with contactless conductivity detection.

Ethane-1,2-diamine (EA) and hexane-1,6-diamine (HA) are two important plastic restricted substances commonly existing in food contact materials. A capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) method has been developed for direct determination of above analytes, and the detection sensitivity has been significantly improved based on electromembrane extraction (EME). Under the optimum conditions, EA and HA could be well separated from their aliphatic diamine homologs as well as the common inorganic cations within 25min. The limits of detection could reach sub-ng/mL level, and good linearity (r>0.998) between peak area and analyte concentration could be obtained at three orders of magnitude. This EME/CE-C4D method provided a novel application for determining these plastic restricted substances in different bottled soft drinks, providing an alternative for the sensitive analyses of diamine substances.

Study on the potential application of salivary inorganic anions in clinical diagnosis by capillary electrophoresis coupled with contactless conductivity detection.

A capillary electrophoresis approach with capacitively coupled contactless conductivity detection method has been developed for the determination of inorganic metabolites (thiocyanate, nitrite and nitrate) in human saliva. Field amplified sample injection, as a simple sample stacking technique, was used in conjunction for online preconcentration of above inorganic anions. A selective separation for the target anions from other coexisting constituents present in saliva could be obtained within 14min in a 10mmol/L His-90mmol/L HAc buffer (pH 3.70) at the separation voltage of -18kV. The limits of detection and limits of quantification of the three analytes were within the range of 3.1-4.9ng/mL (S/N=3) and 10-16ng/mL (S/N=10), respectively. The average recovery data were in the range of 81-108% at three different concentrations. This method provides a simple, rapid and direct approach for metabolite analyses of nitric oxide and cyanide based on noninvasive saliva sample, which presents a potential fast screening tool for clinical test.

Hollow-fiber liquid-phase microextraction coupled with miniature capillary electrophoresis for the trace analysis of four aliphatic aldehydes in water samples.

An environmentally friendly method for the trace analysis of four aliphatic aldehydes as water disinfection byproducts has been developed based on hollow-fiber liquid-phase microextraction followed by miniature capillary electrophoresis with amperometric detection. After derivatization with 2-thiobarbituric acid, four aliphatic aldehydes (formaldehyde, acetaldehyde, propylaldehyde, and butyraldehyde) became detectable by the amperometric detector. Under the optimum conditions, four aliphatic aldehydes can be well separated from the coexisting interferents as well as their homologs (pentanal, glyoxal, and methyl-glyoxal), and the limits of detection (S/N = 3) could reach sub-nanogram-per-milliliter level based on hollow-fiber liquid-phase microextraction. The proposed method has been applied for the analyses of above four aliphatic aldehydes in different water samples such as drinking water, tap water, and river water, and the average recoveries were in the range of 90-113%, providing an alternative to conventional and microchip capillary electrophoresis approaches.

Electromembrane extraction of salivary polyamines followed by capillary zone electrophoresis with capacitively coupled contactless conductivity detection.

Electromembrane extraction (EME) as a novel sample preparation technique was firstly applied for the purification and enrichment of four polyamines mainly present in saliva samples. These four target analytes, putrescine, cadaverine, spermidine, and spermine, were directly determined by CZE with capacitively coupled contactless conductivity detection (CZE-C(4)D) after EME procedure. Several factors affecting extraction efficiency, electrophoretic separation, and detection were investigated. Under the optimum conditions, four polyamines were baseline separated within 22 min, exhibiting a linear calibration over three orders of magnitude (r>0.999); the highest enrichment factor could reach 106-fold (for spermidine), and the LODs were in the range of 1.4-7.0 ng mL(-1). The proposed EME/CZE-C(4)D method has been successfully applied to analyze human saliva samples with recoveries in the range of 78-97%.

Sensitive determination of endogenous hexanal and heptanal in urine by hollow-fiber liquid-phase microextraction prior to capillary electrophoresis with amperometric detection.

Hexanal (Hex) and heptanal (Hep) in human blood have been regarded as potential biomarkers of lung cancer. In this work, a hollow-fiber liquid-phase microextraction (HF-LPME) method has been developed for the preconcentration of these trace aldehydes in urine samples. After derivatization with an electroactive compound 2-thiobarbituric acid, these two non-electroactive aldehydes were converted to electroactive adducts, therefore detectable by capillary zone electrophoresis with amperometric detection (CZE-AD) approach. Experimental conditions of derivatization, extraction, electrophoretic separation and detection were optimized. Under the optimum conditions, the enrichment factors for Hex and Hep could reach 320 and 355, respectively. The limits of detection for Hex and Hep were 2.7 and 0.97 nM, respectively; the average recoveries were in the range of 61-95% and relative standard deviation (RSD) values less than 8.5%. The present method has been applied to quantitative analysis of two biomarkers in human urine in lieu of blood samples, and the assay results showed that the contents of Hex (0.99-6.7 µM) and Hep (2.5-6.4 µM) found in the urine sample of the lung cancer patients were significantly higher than those in the healthy volunteers, liver cancer patients, as well as diabetics. The proposed HF-LPME/CZE-AD method may provide a potential alternative for early non-invasive diagnosis of lung cancer disease.

Fast determination of aldehyde preservatives by miniaturized capillary electrophoresis with amperometric detection.

A novel miniaturized CE with amperometric detection (mini-CE-AD) method has been developed for fast determination of aliphatic aldehyde preservatives, namely formaldehyde and glyoxal, in commodities. After derivatization with an electroactive compound 2-thiobarbituric acid, these two nonelectroactive aldehydes were converted to electroactive adducts, therefore detectable by mini-CE-AD approach. Under the optimum conditions, two aldehydes can be well-separated with the coexisting interferents as well as their homologs (acetaldehyde and methyl-glyoxal), and the LODs (S/N = 3) were achieved at nanogram-per-milliliter level (1.64-2.80 ng/mL) based on the online enrichment method of transient moving chemical reaction boundary. The proposed method has been applied for the analyses of above aldehyde preservatives in different real commodity samples including skincare products, baby lotion, and toothpaste, and the average recoveries were in the range of 94-105%, which should find a wide range of analytical applications as an alternative to conventional and microchip CE approaches.

Hollow-fiber liquid-phase microextraction combined with capillary electrophoresis for trace analysis of sulfonamide compounds.

A hollow-fiber liquid-phase microextraction (HF-LPME) method has been developed for the preconcentration of trace sulfonamides in water samples. Six commonly used sulfonamides including sulfamethazine (SMZ), sulfamerazine (SMR), sulfadiazine (SDZ), sulfadimethoxine (SDM), sulfamethoxazole (SMX), and sulfathiazole (STZ) were determined by CE with electrochemical detection (CE-ED) after microextraction. Several factors that affect extraction efficiency, separation, and detection were investigated. Under the optimum conditions, above sulfonamide compounds could achieve baseline separation within 35min, exhibiting a linear calibration over three orders of magnitude (r(2)≥0.998); the obtained enrichment factors were between 121 (for SDZ) and 996 (for SDM), and the LODs were in the range of 0.033-0.44ng/mL. The proposed HF-LPME/CE-ED method has been applied for the sensitive analyses of the real-world water samples with recoveries in the range of 75.1-109%.