Effect of Temperature and H Flux on the NH3 Synthesis via Electrochemical Hydrogen Permeation.

Ammonia is an indispensable commodity and a potential carbon free energy carrier. The use of H permeable electrodes to synthesize ammonia from N2 , water and electricity, provides a promising alternative to the fossil fuel based Haber-Bosch process. Here, H permeable Ni electrodes are investigated in the operating temperature range 25-120 °C, and varying the rate of electrochemical atomic hydrogen permeation. At 120 °C, a steady reaction is achieved for over 12 h with 10 times higher cumulative NH3 production and almost 40-fold increase in faradaic efficiency compared to room temperature experiments. NH3 is formed with a cell potential of 1.4 V, corresponding to a minimum electrical energy investment of 6.6 kWh kg-1 NH 3 ${{_{{\rm NH}{_{3}}}}}$ . The stable operation is attributed to a balanced control over the population of N, NHx and H species at the catalyst surface. These findings extend the understanding on the mechanisms involved in the nitrogen reduction reaction and may facilitate the development of an efficient green ammonia synthesis process.

Sub/supercritical Fluid Chromatography Purification and Desalting of a Cyclic Dinucleotide STING Agonist.

An efficient and "endotoxin-free" purification of a cyclic dinucleotide (CDN) STING agonist was achieved to produce multigram quantities of pure BMT-390025, an active pharmaceutical ingredient (API), for toxicological studies. A two-step sub/supercritical fluid chromatography (SFC) procedure was developed for the achiral purification and desalting of the polar ionic CDN. A robust SFC process employing methanol-acetonitrile-water with ammonium acetate as co-solvent in CO2 on BEH 2-ethylpyridine was established and scaled up as the first step to achieve a successful purification. The desalting/salt-switching (i.e. removing acetate and acetamide) was conducted using methanol-water with ammonium hydroxide as co-solvent on the same column in the second step to convert the final API to the ammonium salt. Water with additive was essential to eliminating salt precipitation and improving the peak shape and resolution. Due to the extreme hydrophilicity of BMT-390025, 65% of co-solvent was needed to adequately elute the target in both steps. More than 40 g of crude API was purified and desalted producing >20 g of pure BMT-390025 as the ammonium salt which was obtained with a chemical purity of >98.5% and met the endotoxin requirement of <0.1 EU/mg. In addition, >80 g of its penultimate prior to the deprotection of the silyl group was purified at a high throughput of 6.3 g/h (0.42 g/day/g SP).

Large-scale supercritical fluid chromatography purification of unstable STING agonist intermediates.

A regioisomeric mixture of the nucleoside derivative, Intermediate 1, required resolution by preparative supercritical fluid chromatography (SFC) in order to obtain the desired regioisomer as a key intermediate in a STING agonist program. Various chiral columns and solvents including methanol, acetonitrile, isopropanol, and the mixture of acetonitrile and isopropanol as organic modifiers in carbon dioxide at different temperatures were screened to obtain the best regioisomeric resolution. A key issue associated with interconversion between the regioisomers via silyl migration during purification was investigated in methanol, acetonitrile, and the mixture of acetonitrile and isopropanol, and the optimal organic modifier in CO2 was established to mitigate the interconversion to an acceptable level (<5%). Taking into account peak resolution, throughput, interconversion and operation robustness, an efficient SFC method for large-scale purification was successfully developed and scaled up onto a 5 cm I. D. Chiralcel OJ-H column using 25% acetonitrile: isopropanol [1:1 (v/v)] with 0.1% ammonium hydroxide as the modifier in CO2 at a total flow rate of 270 mL/min and a temperature of 30°C. In addition, continual evaporation (i.e. every hour) of the desired isomer fraction stream post-separation ensured minimal further interconversion. A total of 258 grams were separated at a high throughput of 8.6 g/h. Regioisomeric purity of the desired isomer of Intermediate 1 was ≥98.2% and the recovery was ≥90.2%. A similar purification strategy was applied to the regioisomeric resolution of Intermediate 2, an analog of Intermediate 1. In total, 1028 grams of Intermediate 2 were processed at a high throughput of 12.5 g/h on a Viridis BEH 2-EP column. The regioisomeric purity of the desired isomer was ≥96.8% and the recovery was ≥90.7%.

The effect of column history in supercritical fluid chromatography: Practical implications.

Long-term stability of retention times of a wide range of analytes has been evaluated using eight different stationary phases. These were from a single manufacturer to minimize the differences in silanol activity caused by the manufacturing process. The tested stationary phases included bridge ethylene hybrid, 2-ethylpyridine bridge ethylene hybrid with direct modification of silica particles, bidentate crosslinked charged surface hybrid fluorophenyl, bidentate crosslinked high strength silica C18, and propanediol linked phases including diol (pure propanediol linker), and three phases based on diol further modified with 2-picolylamine, diethylamine, and 1-aminoanthracene group. Retention times were monitored at the first injection, after three, nine, twelve months, and after the column regeneration via washing with pure water. The analyses were carried out using three different mobile phases, including methanol, methanol with 10 mmol/L ammonium formate, and methanol with 0.1% ammonium hydroxide. No overall decreasing or increasing trends were observed after evaluating individual contributing parameters such as analyte, stationary phase, and organic modifier. Our results suggest that the silyl-ether formation is not the only factor contributing to changes in the stationary phase pore surface. Indeed, the adsorption of mobile phase additives is probably another significant factor. That was also confirmed by the regeneration procedure using water, which is likely to reverse the silyl-ether formation to achieve the original retention. However, the retention times returned to the original values for all analytes only on three columns. Retention times on other columns remained shifted within ± 15 % RSD depending on the analyte properties and the nature of organic modifier. The retention time variations observed for each analyte group, i.e., acids, bases, and neutrals, were interpreted for each stationary phase. We concluded that the sterically protected surfaces exhibited significantly smaller changes in the retention times. Although the regeneration procedure effect depended on the column type, the results suggested beneficial effect of water. However, as the adsorption of additives on the column surface is an additional factor leading to retention time variations, the recommendation of using only one additive and/or organic modifier in each column will clearly improve the long-term repeatability of the retention times.

Kinetic Behavior of Quaternary Ammonium Hydroxides in Mixed Methane and Carbon Dioxide Hydrates.

This study evaluates the kinetic hydrate inhibition (KHI) performance of four quaternary ammonium hydroxides (QAH) on mixed CH4 + CO2 hydrate systems. The studied QAHs are; tetraethylammonium hydroxide (TEAOH), tetrabutylammonium hydroxide (TBAOH), tetramethylammonium hydroxide (TMAOH), and tetrapropylammonium hydroxide (TPrAOH). The test was performed in a high-pressure hydrate reactor at temperatures of 274.0 K and 277.0 K, and a concentration of 1 wt.% using the isochoric cooling method. The kinetics results suggest that all the QAHs potentially delayed mixed CH4 + CO2 hydrates formation due to their steric hindrance abilities. The presence of QAHs reduced hydrate formation risk than the conventional hydrate inhibitor, PVP, at higher subcooling conditions. The findings indicate that increasing QAHs alkyl chain lengths increase their kinetic hydrate inhibition efficacies due to better surface adsorption abilities. QAHs with longer chain lengths have lesser amounts of solute particles to prevent hydrate formation. The outcomes of this study contribute significantly to current efforts to control gas hydrate formation in offshore petroleum pipelines.

Optimized Extraction of Amikacin from Murine Whole Blood.

Amikacin (Amk) analysis and quantitation, for pharmacokinetics studies and other types of investigations, is conventionally performed after extraction from plasma. No report exists so far regarding drug extraction from whole blood (WB). This can represent an issue since quantification in plasma does not account for drug partitioning to the blood cell compartment, significantly underrating the drug fraction reaching the blood circulation. In the present work, the optimization of an extraction method of Amk from murine WB has been described. The extraction yield was measured by RP-HPLC-UV after derivatization with 1-fluoro-2,4-dinitrobenzene, which produced an appreciably stable derivative with a favorable UV/vis absorption. Several extraction conditions were tested: spiked Amk disulfate solution/acetonitrile/WB ratio; presence of organic acids and/or ammonium hydroxide and/or ammonium acetate in the extraction mixture; re-dissolution of the supernatant in water after a drying process under vacuum; treatment of the supernatant with a solution of inorganic salts. The use of 5% (by volume) of ammonium hydroxide in a hydro-organic solution with acetonitrile, allowed the almost quantitative (95%) extraction of the drug from WB.

Preparation of carbon dots from waste cellulose diacetate as a sensor for tetracycline detection and fluorescence ink.

As one type of the solid wastes, the increasing contamination of waste cellulose diacetate (CDA) from discarded cigarette filters is a growing problem worldwide. Finding a facile and suitable approach to convert the CDA into value-added materials is of significance. Herein, we reported a green, simple and effective method to reuse CDA as precursor for preparing fluorescence N-doped carbon dots (N-CDs) via one-pot hydrothermal carbonization in aqueous solution with low-cost ammonium hydroxide as the passivation agent. The N-CDs showed a quantum yield up to 22.4% with a maximum emission at 415 nm and excitation at 320 nm. Interestingly, the N-CDs exhibited high selectivity toward tetracycline (TC) as their fluorescence was obviously quenched by TC as a result of inner-filter effect. A linear relationship was fabricated over concentration range of 0-80 µM with a detection limit of 0.06 µM. Moreover, the N-CDs could also be applied as fluorescent ink for anti-forgery.

Highly efficient recovery of molybdenum from spent catalyst by an optimized process.

Disposal of spent catalyst in an economical and green way has become a great concern for industrial production. We developed a process including acid leaching, solvent extraction and stripping in order to recycle spent catalyst. In this study, we conducted selective recovery of molybdenum through focus on finding an optimized extraction and stripping process by comparing different extractants and stripping agents. To separate molybdenum from other metals efficiently and figure out the mechanism of extraction process, the five different extractants of methyl trioctyl ammonium chloride, tri-n-octylamine, tris (2-ethylhexyl) amine, bis (2-ethylhexyl) phosphate, and tributyl phosphate with different functional groups were examined; the extraction ability and extraction mechanism of these five extractants were systematically studied under the same system for the first time. It was found that more than 98% of the molybdenum could be extracted with an organic phase consisting of tri-n-octylamine or methyl trioctyl ammonium chloride under the optimal conditions. The result indicated that the tri-n-octylamine and methyl trioctyl ammonium chloride possess excellent molybdenum extraction ability, the extraction capacity of the rest extractants was in the order of bis (2-ethylhexyl) phosphate > tris (2-ethylhexyl) amine > tributyl phosphate. In the stripping process, NH4OH, NaOH, and H2SO4 were chosen as stripping agent to strip the molybdenum from the loaded tri-n-octylamine organic phase. The stripping ability of the three studied stripping agents was in the order NaOH > NH4OH > H2SO4. The Fourier transform infrared (FTIR) spectra showed that the structure of the tri-n-octylamine organic phase was stable during the extraction and stripping process. Results showed that molybdenum could be highly and efficiently recovered by optimized extraction and stripping process. Implications: A series of different extractants and stripping agent have been systematically studied in order to compare their extraction and stripping ability under the same system. Based on the obtained results, an optimized extraction and stripping process was proposed to recycle molybdenum from spent catalyst efficiently. It is possible to dispose spent catalysts in an economic and environmental way by this developed metal recovery process.

n-Butylamine for Improving the Efficiency of Untargeted Mass Spectrometry Analysis of Plasma Metabolite Composition.

A comparative study of the impact of n-butylamine and traditionally used additives (ammonium hydroxide and formic acid) on the efficiency of the electrospray ionization (ESI) process for the enhancement of metabolite coverage was performed by direct injection mass spectrometry (MS) analysis in negative mode. Evaluation of obtained MS data showed that n-butylamine is one of the most effective additives for the analysis of metabolite composition in ESI in negative ion mode (ESI(-)) The limitations of the use of n-butylamine and other alkylamines in the analysis of metabolic composition and a decontamination procedure that can reduce MS device contamination after their application are discussed. The proposed procedure allows the performance of high-sensitivity analysis of low-molecular-weight compounds on the same MS device in both polarities.

Transforming growth factor-ß activation in cell-free extracellular matrix preparations. Commentary.

Transforming growth factor-ß (TGF-ß) is an important regulator of many cellular and immunological functions. It is often deposited in extracellular matrices in a latent form. This commentary is to draw attention to the likelihood that preparing cell-free matrices from tissue cultures by high pH buffers, such as ammonium hydroxide, can activate the TGF-ß. Therefore, cells subsequently seeded onto such matrices may respond to the presence of active TGF-ß in addition to interactions with macromolecular extracellular matrix components.

Electrosynthesis of amino acids from biomass-derivable acids on titanium dioxide.

Seven amino acids were electrochemically synthesized from biomass-derivable α-keto acids and NH2OH with faradaic efficiencies (FEs) of 77-99% using an earth-abundant TiO2 catalyst. Furthermore, we newly constructed a flow-type electrochemical reactor, named a "polymer electrolyte amino acid electrosynthesis cell", and achieved continuous production of alanine with an FE of 77%.

Valorization of sugarcane bagasse by chemical pretreatment and enzyme mediated deconstruction.

After chemical pretreatment, improved amenability of agrowaste biomass for enzymatic saccharification needs an understanding of the effect exerted by pretreatments on biomass for enzymatic deconstruction. In present studies, NaOH, NH4OH and H2SO4 pretreatments effectively changed visible morphology imparting distinct fibrous appearance to sugarcane bagasse (SCB). Filtrate analysis after NaOH, NH4OH and H2SO4 pretreatments yielded release of soluble reducing sugars (SRS) in range of ~0.17-0.44%, ~0.38-0.75% and ~2.9-8.4% respectively. Gravimetric analysis of pretreated SCB (PSCB) biomass also revealed dry weight loss in range of ~25.8-44.8%, ~11.1-16.0% and ~28.3-38.0% by the three pretreatments in the same order. Release of soluble components other than SRS, majorly reported to be soluble lignins, were observed highest for NaOH followed by H2SO4 and NH4OH pretreatments. Decrease or absence of peaks attributed to lignin and loosened fibrous appearance of biomass during FTIR and SEM studies respectively further corroborated with our observations of lignin removal. Application of commercial cellulase increased raw SCB saccharification from 1.93% to 38.84%, 25.56% and 9.61% after NaOH, H2SO4 and NH4OH pretreatments. Structural changes brought by cell wall degrading enzymes were first time shown visually confirming the cell wall disintegration under brightfield, darkfield and fluorescence microscopy. The microscopic evidence and saccharification results proved that the chemical treatment valorized the SCB by making it amenable for enzymatic saccharification.

Chaotropic Effects in Sub/Supercritical Fluid Chromatography via Ammonium Hydroxide in Water-Rich Modifiers: Enabling Separation of Peptides and Highly Polar Pharmaceuticals at the Preparative Scale.

Chromatographic separation, analysis and characterization of complex highly polar analyte mixtures can often be very challenging using conventional separation approaches. Analysis and purification of hydrophilic compounds have been dominated by liquid chromatography (LC) and ion-exchange chromatography (IC), with sub/supercritical fluid chromatography (SFC) moving toward these new applications beyond traditional chiral separations. However, the low polarity of supercritical carbon dioxide (CO2) has limited the use of SFC for separation and purification in the bioanalytical space, especially at the preparative scale. Reaction mixtures of highly polar species are strongly retained even using polar additives in alcohol modifier/CO2 based eluents. Herein, we overcome these problems by introducing chaotropic effects in SFC separations using a nontraditional mobile phase mixture consisting of ammonium hydroxide combined with high water concentration in the alcohol modifier and carbon dioxide. The separation mechanism was here elucidated based on extensive IC-CD (IC couple to conductivity detection) analysis of cyclic peptides subjected to the SFC conditions, indicating the in situ formation of a bicarbonate counterion (HCO3-). In contrast to other salts, HCO3- was found to play a crucial role acting as a chaotropic agent that disrupts undesired H-bonding interactions, which was demonstrated by size-exclusion chromatography coupled with differential hydrogen-deuterium exchange-mass spectrometry experiments (SEC-HDX-MS). In addition, the use of NH4OH in water-rich MeOH modifiers was compared to other commonly used basic additives (diethylamine, triethylamine, and isobutylamine) showing unmatched chromatographic and MS detection performance in terms of peak shape, retention, selectivity, and ionization as well as a completely different selectivity and retention behavior. Moreover, relative to ammonium formate and ammonium acetate in water-rich methanol modifier, the ammonium hydroxide in water additive showed better chromatographic performance with enhanced sensitivity. Further optimization of NH4OH and H2O levels in conjunction with MeOH/CO2 served to furnish a generic modifier (0.2% NH4OH, 5% H2O in MeOH) that enables the widespread transition of SFC to domains that were previously considered out of its scope. This approach is extensively applied to the separation, analysis, and purification of multicomponent reaction mixtures of closely related polar pharmaceuticals using readily available SFC instrumentation. The examples described here cover a broad spectrum of bioanalytical and pharmaceutical applications including analytical and preparative chromatography of organohalogenated species, nucleobases, nucleosides, nucleotides, sulfonamides, and cyclic peptides among other highly polar species.

Isolation and Purification of Pyrazines Produced by Reaction of Cellulosic-Derived Sugars with NH4OH and Selected Amino Acids.

Various pyrazines have been synthesized via reaction of selected cellulosic-derived sugars, ammonium hydroxide and amino acids at 110°C for 2 hours. Different methods of sample cleanup such as liquid-liquid extraction (LLE), liquid-solid extraction, column chromatography and distillation were employed to isolate pyrazines from the reaction mixture. Effective LLE of pyrazines from aqueous solution using either hexane, methyl-t-butyl ether (MTBE) or ethyl acetate required multiple extraction steps with fresh solvent each time. When hexane was used as the extraction solvent, no imidazole derivatives were extracted with the pyrazines. However, when MTBE or ethyl acetate was employed, 4-methyl imidazole was co-extracted and further cleanup was required. Passing the organic solvent extracts through a column of silica revealed that the silica retained the undesirable imidazoles, such as 4-methyl imidazole. A mixture of 90/10 hexane/ethyl acetate as eluting solvent provided the desirable pyrazines, but it also provided a desirable separation of pyrazines as a function of total alkyl substituent content. Distillation of the aqueous reaction mixture was also used to isolate the pyrazines, leaving the undesirable imidazoles in the undistilled portion of the reaction. Additional chromatographic methods were used to isolate pyrazines from the aqueous distillate including a column packed with C18-bonded silica.

Facile ultrasonic synthesized NH2-carbon quantum dots for ultrasensitive Co2+ ion detection and cell imaging.

The amine decorated carbon quantum dots (NH2-CQDs) were synthesized through ultrasonic method from graphite rods derived CQDs and ammonia hydroxide and utilized as the sensing probes for cobalt (II) ions and nucleic acids. The sensing technique was investigated to be the fluorescence quenching effect, which demonstrated linear relationship between cobalt (II) ions concentration and the emission intensity deviation ratio in the concentration range of 50 nM to 40 µM with the detection limit of 12 nM. In brief, this sensitive and selective detection method was confirmed to demonstrate high potential in cobalt (II) ions detection in real samples and nucleic acid sensing in biological cells.

Toward ultrasensitive and fast colorimetric detection of indoor formaldehyde across the visible region using cetyltrimethylammonium chloride-capped bone-shaped gold nanorods as "chromophores".

Plasmonic nanostructures have been broadly used for chemical detections, but their applications are limited by slow detection rates, insufficient visual resolution and sensitivity due to the chemical and structural stability of conventional plasmonic nanomaterials. It is thus essential to develop strategies to enhance the detection kinetics while promoting their excellent plasmonic properties. In this work, a colorimetric assay for HCHO measurement is developed based on the fact that HCHO can react with Tollens' reagent to anisotropically deposit a layer of silver shells onto the bone-shaped gold nanorod (Au NR) cores. Compared to the routine rod-shaped Au NRs, the bone-shaped Au NRs facilitate the deposition of Ag onto the sunken section due to their unique concave structures, giving rise to fast reaction kinetics and detection rate. It is also important to point out that the surface ligand exchange from CTAB to CTAC is helpful to accelerate the deposition of silver onto Au NRs, which significantly shortens the reaction time. The preferential deposition of Ag on the concave Au NRs induces more dramatic morphology changes and therefore promotes the plasmonic shift of the bone-shaped Au NRs and improves the sensing efficiency. Correspondingly, the apparent color of the solution changes from light gray to dark blue, purple, red, orange and finally to yellow as the longitudinal localized surface plasmon resonance (LSPR) band shifts from 710 to 500 nm along with the emergence of a new LSPR band at 400 nm almost covering the full visible region. The colorimetric method developed enables sensitive detection of HCHO with a low detection limit (1 nM), wide linear range (0.1-50 µM), high visual resolution and good specificity against other common indoor gases. It was successfully applied to the detection of gaseous HCHO present in the air collected from a furniture plaza, showing its potential practicality for on-site HCHO analysis.

Single-Molecule Sensing Using Nanopores in Two-Dimensional Transition Metal Carbide (MXene) Membranes.

Label-free nanopore technology for sequencing biopolymers such as DNA and RNA could potentially replace existing methods if improvements in cost, speed, and accuracy are achieved. Solid-state nanopores have been developed over the past two decades as physically and chemically versatile sensors that mimic biological channels, through which transport and sequencing of biomolecules have already been demonstrated. Of particular interest is the use of two-dimensional (2D) materials as nanopore substrates, since these can in theory provide the highest resolution readout (<1 nm of a biopolymer segment) and opportunities for electronic multiplexed readout through their interesting electronic properties. In this work, we report on nanopores comprising atomically thin flakes of 2D transition metal carbides called MXenes. We demonstrate a high-yield (60%), contamination-free, and alignment-free transfer method that involves their self-assembly at a liquid-liquid interface to large-scale (mm-sized) films composed of sheets, followed by nanopore fabrication using focused electron beams. Our work demonstrates the feasibility of MXenes, a class of hydrophilic 2D materials with over 20 compositions known to date, as nanopore membranes for DNA translocation and single-molecule sensing applications.

Utilization of acid hydrolysate of recovered bacterial cell as a novel organic nitrogen source for L-tryptophan fermentation.

In this study, waste bacterial cell (WBC) was recovered and used as an alternative to yeast extract in L-tryptophan fermentation. The effects of sulfuric acid concentration and temperature on the hydrolysis of WBC were optimized and the amino acid content in the waste bacterial cell hydrolysate (WBCH) was increased. Plackett-Burman and Box-Behnken design analysis revealed the optimum composition of the WBCH-based fermentation medium to be 22.47 g/L WBCH, 2.26 g/L KH2PO4, and 1.25 mg/L vitamin H. L-tryptophan yield and productivity with WBCH as the nitrogen source were 52.3 g/L and 2.16 g/L/h, respectively, which were 13% and 18% higher than those obtained with the yeast extract as the nitrogen source. In addition, WBCH did not affect the growth of Escherichia coli during L-tryptophan fermentation. Cost accounting showed that WBCH could be used as a novel and cheap organic nitrogen source for industrial L-tryptophan production.

Combined dilute hydrochloric acid and alkaline wet oxidation pretreatment to improve sugar recovery of corn stover.

Two-stage dilute hydrochloric acid (DA)/aqueous ammonia wet oxidation (AWO) pretreatment was used to recover the sugars of corn stover. The morphology characterizations of samples were detected by SEM, BET and SXT. The results showed that DA-AWO process demonstrated a positive effect on sugar recovery compared to AWO-DA. 82.8% of xylan was recovered in the first stage of DA-AWO process at 120 °C for 40 min with 1 wt% HCl. The second stage was performed under relative mild reaction conditions (130 °C, 12.6 wt% ammonium hydroxide, 3.0 MPa O2, 40 min), and 86.1% lignin could be removed. 71.5% of glucan was achieved with a low enzyme dosage (3 FPU·g-1) in the following enzymatic hydrolysis. DA-AWO pretreatment was effective due to its sufficient hydrolysis of hemicellulose in the first stage and remarkably removal of the lignin in the second stage, resulting in high sugar recovery with a low enzyme dosage.

Development of a micro-solid-phase extraction molecularly imprinted polymer technique for synthetic cannabinoids assessment in urine followed by liquid chromatography-tandem mass spectrometry.

Several molecularly imprinted polymers (MIPs) have been synthesized for the first time using various synthetic cannabinoids (JWH007, JWH015 and JWH098) as template molecules. Ethylene dimethacrylate (EDMA) was used as a functional monomer for all cases. Similarly, divinylbenzene (DVB) and 2,2'-azobisisobutyronitrile (AIBN) were used as cross-linker and initiator, respectively. The prepared MIPs have been fully characterized and evaluated as new selective adsorbents for micro-solid phase extraction (µ-SPE) of synthetic cannabinoids in urine. The developed MIP-µ-SPE devices consisted of a polypropylene (PP) porous membrane containing the adsorbent (novel porous membrane protected micro-solid phase extraction based on a cone-shaped device) for operating in batch mode, which allowed a fast and integrated extraction-cleanup procedure. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used for quantifying the analytes after MIP-µ-SPE. The best performances were obtained for MIPs prepared from JWH015 as a template. Optimum loading conditions were found to be urine pH of 5.0 and adsorption time of 8.0 min under mechanical (orbital-horizontal) stirring at 100 rpm. The composition of the eluting solution consisted of 75:20:5 heptane/2-propanol/ammonium hydroxide. The elution was assisted by ultrasounds (37 kHz, 325 W) for 8.0 min. In addition, studies regarding selectivity have also been addressed for several drugs of abuse under optimized loading/adsorption conditions. Validation of the method showed good precision and analytical recovery by intra-day and inter-day assays (RSD values lower than 7 and 10% for intra-day and inter-day precision, and within the 83-100% range for intra-day and inter-day analytical recovery).