Aqueous Formic Acid Research Articles

Toxicokinetics of diisobutyl phthalate and its major metabolite, monoisobutyl phthalate, in rats: UPLC-ESI-MS/MS method development for the simultaneous determination of diisobutyl phthalate and its major metabolite, monoisobutyl phthalate, in rat plasma, urine, feces, and 11 various tissues collected from a toxicokinetic study

The aim of this study was to explore the toxicokinetics of diisobutyl-phthalate (DiBP) and its major metabolite, monoisobutyl-phthalate (MiBP), by developing a UPLC-ESI-MS/MS method for simultaneously measuring DiBP and MiBP in rat plasma, urine, feces, and 11 different tissues. For the experiment, 0.1% (v/v) aqueous formic acid and acetonitrile mobile phase by gradient elution at a flow rate of 0.3 mL/min, equipped with a KINETEX core-shell C18-column (50 × 2.1 mm, 1.7 μm), was used to completely separate analytes. The mass transitions were m/z 279.1 → 149.0 for DiBP, 221.0 → 77.0 for MiBP, and 283.2 → 153.0 for DiBP-d4 as an internal standard. The developed assay had lower limits of quantification of 0.01 ng/mL for DiBP and 0.1 ng/mL for MiBP at all biological matrices. Toxicokinetics of DiBP were characterized by extensive distribution, short half-life, and high clearance. DiBP was rapidly metabolized to MiBP, with MiBP levels consistently exceeding the DiBP levels. Distribution of MiBP to tissues was considerable. The developed analytical method satisfied international criteria and was successfully applied to toxicokinetic studies after oral and intravenous administration of DiBP to rats. Findings of this study may be useful for evaluating the external exposure and toxic potential of DiBP and its metabolite in risk assessment.

Production of 5-(formyloxymethyl)furfural from biomass-derived sugars using mixed acid catalysts and upgrading into value-added chemicals

In this work, 5-(formyloxymethyl)furfural (FMF) has been produced from biomass-derived hexose sugars within a biphasic reaction mixture consisting of aqueous formic acid (85%), a strong Brønsted acid catalyst, and 1,2-dichloroethane as an organic extractant. Using a combination of aqueous hydrobromic acid and formic acid, under optimized condition (80 °C, 8 h, 10 wt% substrate loading), 68% isolated yield of FMF was obtained from fructose. FMF has been demonstrated as a renewable chemical building block for the synthesis of renewable chemicals of commercial significance such as 5-methylfurfural, 2,5-diformylfuran, and 2,5-furandicarboxylic acid in good to excellent isolated yields.

Simultaneous determination of fourteen components of Gumiganghwal-tang tablet in human plasma by UPLC-ESI-MS/MS and its application to pharmacokinetic study

Gumiganghwal-tang is a traditional herbal medicine widely used for its anti-inflammatory, analgesic, and antipyretic effects. However, the safety and efficacy of its active ingredients based on an in vivo pharmacokinetic (PK) study have yet been investigated. We have established a sensitive and accurate UPLC-ESI-MS/MS method and conducted a PK study on 14 constituents of Gumiganghwal-tang through human plasma analysis. Analytical conditions were optimized according to the physicochemical properties of the 14 compounds to facilitate efficient separation and eliminate overlap or interference between peaks. KINETEX-C18 and Inertsil-C8 columns were used as UPLC stationary phases, and acetonitrile and aqueous formic acid were used as mobile phases. All the analytes were quantified with a triple quadrupole mass spectrometer using electrospray ionization in multiple reaction monitoring mode. The chromatograms of 14 bioactive compounds showed excellent elution and sensitivity, and each peak was selectively separated and quantified without interference with each other or impurities. The established analytical method was based on international guidelines and was successfully used to perform PK studies of 14 herbal ingredients in humans after oral administration with Gumiganghwal-tang tablets. The oral absorption of most active components of Gumiganghwal-tang was relatively rapid and remained considerably long in the body to be quantified in plasma up to 48 h after administration.

Online Liquid Microextraction Coupled with HPLC-ABTS for Rapid Screening of Natural Antioxidants: Case Study of Three Different Teas.

In the present study, an online liquid extraction coupled with high-performance liquid chromatography-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (HPLC-ABTS) system for rapid screening of antioxidants in tea samples was proposed. As an example, the tea samples were firstly extracted by online HPLC extractor with mobile phase at 70°C, then the hyphenated HPLC-ABTS was used for the chromatographic separation on a Poroshell EC C18 column by 0.3% aqueous formic acid and acetonitrile with a gradient elution at 1.5mL·min-1, and the UV and antioxidant chromatograms with detection wavelengths at 270nm and 750nm were recorded, respectively. The established system integrated the processes of online HPLC sample extraction, HPLC separation and online antioxidants detection, the total analysis time of which was <20min. The developed method was successfully applied to samples of green tea, oolong tea and black tea. As a result, 11 antioxidants were found in tea samples, including gallocatechin, epigallocatechin, catechin, chlorogenic acid, epicatechin, epigallocatechingallate, epicatechingallate, rutin, 1,4,6-trigalloylglucose, quercetin-3-glycoside and kaempferol-3-glucoside. The combined online liquid microextraction and online HPLC-ABTS method is a rapid and green approach for the quality evaluation of tea.

Comparative Analysis of Free Amino Acids and Nucleosides in Different Varieties of Mume Fructus Based on Simultaneous Determination and Multivariate Statistical Analyses.

Mume Fructus (MF) contains a variety of organic acids, free amino acids, and nucleoside components, and studies have not yet analyzed the relationship between the components of free amino acids and nucleosides with the varieties of MF. A rapid and sensitive method was established for simultaneous determination of 21 free amino acids and 9 nucleosides in MF by ultrafast liquid chromatography-mass spectrometry. The analysis was carried out on a Waters XBridge Amide column (100 mm × 2.1 mm, 3.5 μm) with elution by the mobile phase of 0.2% aqueous formic acid (A) and 0.2% formic acid acetonitrile (B) at a flow rate of 0.2 mL/min with 1 μL per injection. The column temperature was maintained at 30°C. The target compounds were analyzed by the positive ion multiple reaction monitoring (MRM) mode. The comprehensive evaluation of the samples was carried out by principal component analysis (PCA) and technique for order preference by similarity to an ideal solution (TOPSIS) analysis. Results showed the method could simultaneously determine 30 components in MF. The content of total analytes in six mainstream varieties was different, exhibited the order Nangao > Daqingmei > Zhaoshuimei > Yanmei > Shishengme > Baimei, and aspartic acid and adenosine were the most abundant amino acid and nucleoside. PCA and OPLS-DA could easily distinguish the samples, and 11 components could be chemical markers of sample classification. TOPSIS implied that the quality of Nangao and Daqingmei was superior to the other varieties. The results could provide a reliable basis for quality evaluation and utilisation of medicinal and edible MF.

Mechanistic insights on aqueous formic acid dehydrogenation over Pd/C catalyst for efficient hydrogen production

Efficient hydrogen production is one of the most important issues in the future energy economy. Dehydrogenation of formic acid has been extensively investigated for safe and easy hydrogen production. Thereby, various catalysts have been developed for aqueous formic acid dehydrogenation (FAD) reaction to efficiently produce hydrogen. However, there is still a lack of understanding of the reaction mechanism. Herein, to fundamentally comprehend the aqueous FAD reaction mechanism, we prepared Pd/C catalyst and performed controlled catalytic tests. The results demonstrated that the aqueous FAD reaction occurs through the formate anion dehydrogenation pathway. DFT calculation explained this by the observation that the charge of formate anion significantly mitigates the activation barrier of H-COO bond cleavage. In addition, computational prediction combined with kinetic isotope effect experiments verified that combinative desorption of hydrogen is the rate-determining step of FAD.

Pharmacokinetic comparison with different assays for simultaneous determination of cis-, trans-cefprozil diastereomers in human plasma

The purpose of this study was to compare pharmacokinetic (PK) parameters obtained using two newly developed assays, HPLC-UV and UPLC-ESI-MS/MS. Selection of assay and results obtained therefrom are very important in PK studies and can have a major impact on the PK-based clinical dose and usage settings. For this study, we developed two new methods that are most commonly used in biosample analysis and focused on PK parameters obtained from them. By HPLC-UV equipped with a Luna-C8 column using UV detector, cefprozil diastereomers were separated using water containing 2% (V/V) acetic acid and acetonitrile as a mobile phase. By UPLC-ESI-MS/MS equipped with a HALO-C18column, cefprozil diastereomers were separated using 0.5% (V/V) aqueous formic acid containing 5 mM ammonium-formate buffer and methanol as a mobile phase. Chromatograms showed high resolution, sensitivity, and selectivity without interference by plasma constituents. Both intra- and inter-day precisions (CV, %) were within 8.88% for HPLC-UV and UPLC-ESI-MS/MS. Accuracy of both methods was 95.67%–107.50%. These two analytical methods satisfied the criteria of international guidance and could be successfully applied to PK study. Comparison of PK parameters between two assays confirmed that there is a difference in the predicted minimum plasma concentrations at steady state, which may affect clinical dose and usage settings. Furthermore, we confirmed possible correlation between PK parameters and various biochemical parameters after oral administration of 1000 mg cefprozil to humans.

Simultaneous determination of ferulic acid, paeoniflorin, and albiflorin in rat plasma by ultra-high performance liquid chromatography with tandem mass spectrometry: Application to a pharmacokinetic study of Danggui-Shaoyao-San.

A rapid, selective, and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry method was developed for simultaneous determination of ferulic acid, paeoniflorin, and albiflorin, the major active constituents of Danggui-Shaoyao-San, in rat plasma using geniposide as the internal standard. The plasma samples were processed by protein precipitation with acetonitrile, and then separated on a Shim-Pack XR-ODS C18 column (75mm × 3.0mm, 2.2 μm) using gradient elution program with a mobile phase consisting of 0.1% aqueous formic acid and acetonitrile at a flow rate of 0.4mL/min. The detection was achieved on a 3200 QTRAP mass spectrometer equipped with electrospray ionization source in negative ionization mode. Quantification was performed using multiple reaction monitoring mode by monitoring the fragmentation of m/z 192.9→134.0 for ferulic acid, m/z 525.0→120.9 for paeoniflorin, m/z 525.2→121.0 for albiflorin, and m/z 433.1→225.1 for the internal standard, respectively. The calibration curve was linear in the range of 5-2500ng/mL for all the three analytes (r ≥ 0.9972) with the lower limit of quantitation of 5ng/mL. The intraday and interday precisions were below 12.1% for all the analytes in terms of relative standard deviation, and the accuracy was within ±11.5% in terms of relative error. The extraction recovery, matrix effect and stability were satisfactory in rat plasma. The validated method was successfully applied to a pharmacokinetic study of ferulic acid, paeoniflorin, and albiflorin after oral administration of Danggui-Shaoyao-San to rats.

Simultaneous Determination of 12 Marker Components in Yeonkyopaedok-san Using HPLC–PDA and LC–MS/MS

Yeonkyopaedok-san is a traditional Korean medicine used in the early treatment of boils. In the present study, its 12 marker components for quality control were determined using high-performance liquid chromatography (HPLC) with photodiode array detection and ultra-performance liquid chromatography–mass spectrometry with tandem mass spectrometry (UPLC–MS/MS). The investigated 12 marker components of Yeonkyopaedok-san were as follows: 3-caffeoylquinic acid, cimifugin 7-glucoside, liquiritin apioside, ferulic acid, narirutin, 5-O-methylvisammioside, naringin, neohesperidin, oxypeucedanin hydrate, arctigenin, glycyrrhizic acid, and 6-gingerol. The analytical column used for the separation of the 12 marker analytes in Yeonkyopaedok-san was a Waters SunFire C18 column (4.6 mm × 250 mm, 5 μm). The two mobile phases used were 0.1% (v/v) aqueous formic acid and 0.1% (v/v) formic acid in acetonitrile. In the UPLC–MS/MS analysis, all components were separated using a Waters ACQUITY UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm). The two mobile phases used were 0.1% (v/v) aqueous formic acid and acetonitrile. The coefficient of determination of the calibration curves in both analysis systems showed good linearity (&gt;0.99). The amounts of the 12 marker components in Yeonkyopaedok-san determined using HPLC–photodiode array detection and UPLC–MS/MS analyses were found to be 0.14–9.00 mg/g and 2.35–853.11 μg/g, respectively.

Blood and Plasma Volumetric Absorptive Microsampling (VAMS) Coupled to LC-MS/MS for the Forensic Assessment of Cocaine Consumption.

Reliable, feasible analytical methods are needed for forensic and anti-doping testing of cocaine and its most important metabolites, benzoylecgonine, ecgonine methyl ester, and cocaethylene (the active metabolite formed in the presence of ethanol). An innovative workflow is presented here, using minute amounts of dried blood or plasma obtained by volumetric absorptive microsampling (VAMS), followed by miniaturized pretreatment by dispersive pipette extraction (DPX) and LC-MS/MS analysis. After sampling 20 µL of blood or plasma with a VAMS device, the sample was dried, extracted, and loaded onto a DPX tip. The DPX pretreatment lasted less than one minute and after elution with methanol the sample was directly injected into the LC-MS/MS system. The chromatographic analysis was carried out on a C8 column, using a mobile phase containing aqueous formic acid and acetonitrile. Good extraction yield (> 85%), precision (relative standard deviation, RSD < 6.0%) and matrix effect (< 12%) values were obtained. Analyte stability was outstanding (recovery > 85% after 2 months at room temperature). The method was successfully applied to real blood and plasma VAMS, with results in very good agreement with those of fluid samples. The method seems suitable for the monitoring of concomitant cocaine and ethanol use by means of plasma or blood VAMS testing.

UPLC-Q-TOF-MS Study of the Mechanism of THSWD for Breast Cancer Treatment.

Taohong Siwu decoction (THSWD) is a classic traditional Chinese medicine (TCM) prescription that is widely used in the clinical treatment of gynecological and cerebrovascular diseases. Here we used a method that coupled ultra-performance liquid chromatography to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) in which both positive and negative ion modes were established to investigate the major constituents in THSWD. A Waters ACQUITY UPLC BEH C18 column (2.1 mm×100 mm, 1.7 μm) was used to separate the aqueous extract of THSWD. The mobile phase consisted of 0.1% aqueous formic acid (A) and acetonitrile (B). Ninety-five components were identified in two different ion modes, including aromatic acids, flavones, polysaccharides, volatile oils monoterpene glycosides, aromatic cyanogenic glycosides, and others. Pathological changes in tumors and serum expression of interleukin-4 in a mouse model of breast cancer were detected after THSWD treatment. The results showed that THSWD had obvious therapeutic effects. This study establishes a material basis for the use of THSWD in the treatment of breast cancer.

Rapid quantitative analysis of 18 chemical constituents in HuangQi JianZhong Tang based on UHPLC-MS.

A rapid, highly sensitive, and specific analytical method using ultra-high-performance liquid chromatography-triple quadruple MS was developed to quantitatively measure 18 chemical constituents in Huangqi Jianzhong Tang (HQJZ), a famous traditional Chinese medicine formula. Chromatographic separation was performed on a Waters ACQUITY UPLC HSS T3 column (2.1 mm × 100 mm, 1.8 μm) with a gradient mobile phase (A: 0.1% aqueous formic acid and B: acetonitrile) at a flow rate of 0.25 mL/min. The chromatographic peaks of 18 components were identified by comparing with the reference compounds. Multiple reaction monitoring was employed for quantitative analysis of the components. Seven batches of HQJZ samples were analyzed with a good linear regression relationship (R2 , .9978-.9993), precisions [relative standard deviation (RSD), 0.90%-3.60%], repeatability (RSD, 2.50%-4.00%), stability (RSD, 1.00%-4.00%), and recovery (96.10%-104.30%). Based on this established method, the present study offered a highly sensitive, specific, and rapid determination method for identification of 18 compounds, which greatly promoted the systemic quality control of HQJZ.

Nucleoside Isolation Performance of Ti4+/Zr4+ Immobilized Polydopamine Coated, Monodisperse-Porous Titania Microbeads

A Ti4+/Zr4+ ion immobilized sorbent was developed by starting from monodisperse-porous titania microbeads, for the isolation of nucleosides via immobilized metal affinity chromatography (IMAC). For the synthesis of IMAC sorbent, the monodisperse-porous titania microbeads were coated with a polydopamine (PDA) layer. PDA coated titania microbeads were then interacted with TiCl4 or ZrOCl2 solution for the immobilization of Ti4+ or Zr4+ ions onto the PDA layer. Five nucleosides (adenosine, uridine, cytidine, thymidine and guanosine) were individually adsorbed onto Ti4+ or Zr4+ immobilized titania microbeads in aqueous buffer in a pH range of 4–9. The desorption of nucleosides was performed in an aqueous formic acid solution. The nucleoside isolation performance of Ti4+ immobilized sorbent was also compared with Zr4+ immobilized sorbent, PDA coated titania and bare titania microbeads. The highest equilibrium adsorptions and the highest desorption yields were obtained with Ti4+ immobilized sorbent for all nucleosides. It was demonstrated that pH 7 was found as the most appropriate for the adsorption of all nucleosides onto Ti4+ immobilized sorbent, which was also close to the physiological pH of urine. The highest equilibrium adsorption was observed with adenosine as 12.67 mg adenosine/g Ti4+ immobilized sorbent. Almost quantitative desorption yields were achieved with all nucleosides adsorbed in a wide range of pH onto Ti4+ immobilized sorbent. With respect to the similar sorbents developed previously, we believe that the proposed sorbent is a promising candidate for being a stationary phase particularly for the construction of micro-column based IMAC systems used in the continuous isolation of nucleosides.

Magnetically recoverable nanocatalyst based on N-heterocyclic ligands: efficient treatment of environmental pollutants in aqueous media

The fabrication of aminotetrazole–palladium(II) complex immobilized on silica-encapsulated Fe3O4 magnetic nanoparticles is described with full characterization using XRD, TGA–DTG, EDS, TEM, FESEM, VSM and FTIR spectroscopy. This prepared core–shell entity has been explored as a highly efficient reusable nanocatalyst with superior stability and high catalytic activity in the reduction of hexavalent chromium [Cr(VI)], nitroarenes and azo dyes compared to other reported Pd-based nanocatalysts. The catalytic activity of the catalyst for the reduction of Cr(VI), 2,4-dinitrophenylhydrazine, 4-nitrophenol, methyl orange, Congo red, nigrosin and rhodamine B with sodium borohydride (NaBH4) aqueous solution or formic acid is evaluated by UV–Vis spectroscopy. The present study illustrates an unprecedented example of arylaminotetrazole grafted on magnetic nanoparticles as an excellent magnetically recoverable catalyst which can be recycled seven times without any meaningful changes in the reaction time.

Analysis of complex mixtures of polyglycerol fatty esters using liquid chromatography and high-resolution mass spectrometry: Retention, structural and relative composition study

Polyglycerol esters (PGEs), produced by esterification of fatty acids on polyglycerols, were analysed by High Resolution Mass Spectrometry (HRMS), HPLC-MS and U-HPLC-MS. A structural study of PGEs in 4 samples synthesised by the Gattefossé company was carried out using an elemental analysis of HRMS spectra and modelling of all probable isomers and cyclic structures. The results were used to construct a structural database of all species present in the 4 samples. After an assessment of the selectivity of 5 reversed phase columns: Aeris Widepore XB-C8, 3.6 µm, 2.1 × 150 mm (Phenomenex), Acquity CSH C18 1.7 µm 2.1 × 50 mm, Acquity CSH Phenyl-Hexyl 1.7 µm 2.1 × 50 mm, Acquity CSH Fluoro-Phenyl 1.7 µm 2.1 × 50 mm (Waters Co.) and Kinetex F5 1.7 µm 2.1 × 100 mm (Phenomenex), HPLC-MS and U-HPLC-MS analyses were performed on an Aeris Widepore XB-C8 (Phenomenex) column (HPLC) and Acquity CSH Fluoro-Phenyl (Waters) column (U-HPLC) with aqueous formic acid /acetonitrile in gradient mode. The separation was optimised with 10 min (HPLC) and 5 min (U-HPLC) of gradient. The detection, performed on a QDA detector (Waters), produced extracted ion chromatograms (XICs) based on all adducts identified in the HRMS analysis. HPLC and U-HPLC analyses showed the different mono- and di-ester species and provided relative quantification of all identified constituents. The combined analyses of the HRMS, HPLC-MS and U-HPLC-MS results were used to compare the different PGE batches and quantify the molecular constituents according to their relative abundance, for these complex mixtures. With HPLC and U-HPLC analyses, using 2 different gradient times and 2 different selectivity columns, and comparing the retention factors and log P of the different species, it was possible to link structural identification and relative quantification of all PGEs identified in the samples.

Palladium nanoparticles stabilized on a novel Schiff base modified Unye bentonite: Highly stable, reusable and efficient nanocatalyst for treating wastewater contaminants and inactivating pathogenic microbes

Efficient decoration and characterization of highly catalytic, active Pd nanoparticles (NPs) onto a novel Schiff base modified Unye bentonite (UN-Sch) with high coordination performance of structurally defined 2-pyrrolaldehyde ligands against palladium ions (Pd NPs@UN) have been described. Amine modified UN/Pd NPs were fabricated via a facile multi-step approach without utilizing any additional reducing agents. To check the applicability of the synthesized Pd NPs@UN as highly active nanocatalysts in water and wastewater treatment, the reduction of highly toxic compounds such as 4-nitrophenol (4-NP), hexavalent chromium [Cr(VI)], Rhodamine B (RhB), potassium hexacyanoferrate(III) (K3[Fe(CN)6]) and congo red (CR) at ambient temperature in eco-friendly media has been investigated. The surface nature of Unye bentonite was altered after modification, leading to notable increase in the catalytic properties. The ensuing Pd NPs@UN demonstrated superior catalytic prowess (100% conversion within a few seconds for the aforementioned pollutants), excellent stability (~4 months) and superior recyclability (~96% yield after seven successive cycles). Notably, the present procedure is a clean and green one in which aqueous sodium borohydride (NaBH4) or formic acid (HCOOH) are used as reducing agents in the absence of any toxic reductants. Moreover, the results showed that Pd NPs@UN was effective against fungi and bacteria.

Development and Validation of a Liquid Chromatography–Tandem Mass Spectrometry Method for Multiresidue Determination of 25 Herbicides in Soil and Tobacco

In the cultivation of tobacco, crop rotation patterns, such as tobacco/rice or tobacco/corn, are widely used. However, the use of herbicides in the rice or corn phase can lead to their being taken in during the tobacco phase by inner conduction action. In the present study, to monitor the use of herbicides in tobacco, a sensitive and simple analytical method coupled with liquid chromatography-tandem mass spectrometry (LC–MS/MS) has been established for determination of 25 herbicides in soil as well as fresh and flue-cured tobacco leaf. The herbicides analyzed include six aryloxy phenoxy propionate herbicides (APPs) and 19 sulfonylureas herbicides (SUs). The samples were extracted using acetonitrile and purified using C18 sorbent before analysis. Optimum separation of the analytes was achieved using an Agilent Eclipse XDB-C18 column at 40 °C and gradient elution with acetonitrile and 0.1% aqueous formic acid as the mobile phase at a flow rate of 0.8 mL min−1. The limits of quantification and detection are in the ranges 0.08–1.00 mg kg−1 and 0.024–0.30 mg kg−1, respectively, and matrix effects in the range − 70 to 50% were achieved. The recovery rates obtained from spiked soil and tobacco leaf samples ranged from 72.32 to 116.83% with intra-day and inter-day relative standard deviations of 0.44–11.55%. In addition, the method developed was applied to the determination of herbicides residues in actual soil and tobacco samples, revealing that the proposed method can detect trace amounts of APPs and SUs in soil as well as in fresh and flue-cured tobacco leaf.

Valorization of Carbohydrates of Agricultural Residues and Food Wastes: A Key Strategy for Carbon Conservation

The complete conservation of the carbon, hydrogen, and oxygen atoms of cellulose and starch can theoretically be achieved by their conversion to levulinic and formic acids. Similarly, hemicellulose can be converted to furfural and water with 100% atom economy. The valorization of carbohydrates of agricultural residues (banana-, orange-, and potato-peels, corn leaf and root, and rice husk), potential components of raw food wastes (corn, rice, potato, lettuce, onion, leek, vegetable, bean, and tomato), and cooked food wastes (rice noodle, spaghetti, risotto, noodle, bread, and biscuit) was demonstrated in the presence of sulfuric acid at 130 °C in γ-valerolactone as the green solvent to yield levulinic and formic acids as the two main products. Levulinic acid was also produced from furfural by its transfer hydrogenation with formic acid to furfuryl alcohol in the presence of Shvo’s catalyst followed by its acid catalyzed conversion to levulinic acid. Neutralization of the sulfuric acid in the reaction mixture with ammonium hydroxide resulted in an aqueous ammonium sulfate phase and a γ-valerolactone rich organic phase. Due to the salting out effect of the ammonium sulfate in the aqueous phase, levulinic acid and formic acid partitioned to the γ-valerolactone rich organic phase at >99.8% and >97.1%, respectively. The transfer hydrogenation of levulinic acid with formic acid in the presence of the Shvo’s catalyst resulted in the formation of 4-hydroxyvaleric acid, which readily underwent dehydration to yield γ-valerolactone, a green and sustainable liquid. The possibility of converting C₅- and C₆-carbohydrates to levulinic acid or γ-valerolactone is a great opportunity for carbon conservation with a carbon-economy higher than that for butanol or ethanol.

Quantitative ultra-high-performance liquid chromatography-tandem mass spectrometry for determination of dexmedetomidine in pediatric plasma samples: Correlation with genetic polymorphisms.

Dexmedetomidine is an important sedative agent administered as premedication to achieve procedural sedation in children. To describe the correlation between the genetic state and the concentration of dexmedetomidine, it is necessary to develop a specific, time-saving and economical method for detection of dexmedetomidine in plasma samples. In this work, an ultra-high-performance liquid chromatography (UHPLC)-tandem mass spectrometry method has been established and validated for detection of dexmedetomidine in plasma from pediatric population. After a simple liquid-liquid extraction with an organic solution, the analytes were separated on an ACQUITY BEH C18 column (2.1 mm × 50 mm, 1.7 μm particle size) by gradient elution with the mobile phase of acetonitrile and 1‰ aqueous formic acid (flow rate 0.3 mL min-1 ). Mass spectrometry measurements were performed under the positive selected reaction monitoring and the mass transitions monitored were m/z 201.3 → 95.1, 204.2 → 98.0 for dexmedetomidine and deuterated medetomidine (internal standard), respectively. Validation of the method based on China Food and Drug Administration guidelines showed acceptable selectivity. The UHPLC method employed a stable isotope-labeled internal standard, showed good specificity and was successfully used to detect dexmedetomidine in plasma samples from 260 pediatric patients. A subsequent application of this method to a pharmacogenetic study was also described. Importantly, this is the first study to report the correlation between CYP2A6 rs835309 activity and concentration of dexmedetomidine.

An HPLC–PDA method for determination of alectinib concentrations in the plasma of an adolescent

Alectinib is a central nervous system-active small molecule anaplastic lymphoma kinase (ALK) inhibitor that is effective in the treatment of patients with ALK positive tumors, including advanced non-small cell lung cancers and lymphomas. A simple, isocratic high-performance liquid chromatography–photo diode array detection (HPLC–PDA) assay for measurement of alectinib in human plasma is described. Alectinib is extracted from the plasma matrix by addition of methanol, followed by centrifugation and acidification with 0.1% formic acid. It elutes with a run time of 4.6 min using a 250 mm × 4.6 mm RP-C18 column with 0.1% aqueous formic acid and methanol (35:65, v/v) and a flow rate of 1 mL/min. Detection was at 339 nm. Linear calibration plots were achieved in the range of 0.1–20 μg/mL for alectinib (r2 = 0.9996). With limits of detection and quantification of 0.05 and 0.1 μg/mL, respectively, and excellent precision (%CV &lt; 10%), accuracy (bias &lt; ±12%), and recovery (&gt;97%) within the 1–20 μg/mL concentration range, this assay was suitable for measuring pre-dose alectinib concentrations in an adolescent receiving 600-mg doses twice daily.