New concept of positive photosensitive polyimide: Reaction development patterning (RDP)

A soluble multiblock copolyimide without specific functional groups such as OH and COOH was prepared by a direct one‐pot polycondensation of two types of dianhydrides and diamines in the presence of γ‐valerolactone/pyridine catalyst using N‐methylpyrrolidone (NMP)/toluene mixture as a solvent. The polyimide film containing the photosensitive agent diazonaphthoquinone (DNQ) compound gave positive‐tone behavior by UV irradiation, followed by development in a mixture of ethanolamine/NMP/H₂O (1/1/1 by weight). The scanning electron microscopic photograph of the resultant image showed fine patterns with about 20 μm film thickness. Its pattern forming was based on the photorearrangement of diazonaphthoquinone, a process in which the ring‐opening reaction of imide units of the polyimide with the amine used as a developer and the following degradation of the polymer are induced. Such a new imaging technique combines principles of photolithography and etching of a polyimide to give, what we call, reaction development patterning in which the main chemical reactions directly related to the pattern formation occur during development. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3451–3463, 2001     

Chiral SiO2 and Ag@SiO2 Materials Templated by Complexes Consisting of Comblike Polyethyleneimine and Tartaric Acid

A facile avenue to fabricate micrometer‐sized chiral (L ‐, D ‐) and meso‐like (dl ‐) SiO₂ materials with unique structures by using crystalline complexes (cPEI/tart), composed of comblike polyethyleneimine (cPEI) and L ‐, D ‐, or dl ‐tartaric acid, respectively, as catalytic templates is reported. Interestingly, both chiral crystalline complexes appeared as regularly left‐ and right‐twisted bundle structures about 10 μm in length and about 5 μm in diameter, whereas the dl ‐form occurred as circular structures with about 10 μm diameter. Subsequently, SiO₂@cPEI/tart hybrids with high silica content (>55.0 wt %) were prepared by stirring a mixture containing tetramethoxysilane (TMOS) and the aggregates of the crystalline complexes in water. The chiral SiO₂ hybrids and calcined chiral SiO₂ showed very strong CD signals and a nanofiber‐based morphology on their surface, whereas dl ‐SiO₂ showed no CD activity and a nanosheet‐packed disklike shape. Furthermore, metallic silver nanoparticles (Ag NPs) were encapsulated in each silica hybrid to obtain chiral (D and L forms) and meso‐like (dl form) Ag@SiO₂ composites. Also, the reaction between L ‐cysteine (Lcys) and these Ag@SiO₂ composites was preliminarily investigated. Only chiral L ‐ and D ‐Ag@SiO₂ composites promoted the reaction between Lcys and Ag NPs to produce a molecular [Ag–Lcys]_n complex with remarkable exciton chirality, whereas the reaction hardly occurred in the case of meso‐like (dl ‐) Ag@SiO₂ composite.     

Development and validation of a sensitive liquid‐chromatography tandem mass spectrometry assay for mycophenolic acid and metabolites in HepaRG cell culture: Characterization of metabolism interactions between p‐cresol and mycophenolic acid

Mycophenolic acid (MPA), a frequently used immunosuppressant, exhibits large inter‐patient pharmacokinetic variability. This study (a) developed and validated a sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay for MPA and metabolites [MPA glucuronide (MPAG) and acyl‐glucuronide (AcMPAG)] in the culture medium of HepaRG cells; and (b) characterized the metabolism interaction between MPA and p‐cresol (a common uremic toxin) in this in vitro model as a potential mechanism of pharmacokinetic variability. Chromatographic separation was achieved with a C₁₈ column (4.6 × 250 mm,5 μm) using a gradient elution with water and methanol (with 0.1% formic acid and 2 mm ammonium acetate). A dual ion source ionization mode with positive multiple reaction monitoring was utilized. Multiple reaction monitoring mass transitions (m/z) were: MPA (320.95 → 207.05), MPAG (514.10 → 303.20) and AcMPAG (514.10 → 207.05). MPA‐d₃ (323.95 → 210.15) and MPAG‐d₃ (517.00 → 306.10) were utilized as internal standards. The calibration curves were linear from 0.00467 to 3.2 μg/mL for MPA/MPAG and from 0.00467 to 0.1 μg/mL for AcMPAG. The assay was validated based on industry standards. p‐Cresol inhibited MPA glucuronidation (IC₅₀ ≈ 55 μm ) and increased MPA concentration (up to >2‐fold) at physiologically relevant substrate‐inhibitor concentrations (n = 3). Our findings suggested that fluctuations in p‐cresol concentrations might be in part responsible for the large pharmacokinetic variability observed for MPA in the clinic.     

Water‐Developable Poly(2‐oxazoline)‐Based Negative Photoresists

Copoly(2‐oxazoline)‐based photoresists are prepared from pEtOx₈₀Bu⁼Ox₂₀ and pPhOx₈₀Dc⁼Ox₂₀ , respectively, a tetrathiol, and a photosensitive initiator. It is possible to prepare copoly(2‐oxazoline)s bearing unsaturated side chains in a microwave reactor on a decagram scale in reaction times of 100 min or shorter. UV irradiation of dried polymer films through a quartz mask induces the thiol‐ene reaction in the illuminated areas. Subsequent development of the polymer films in halogen‐free solvents reproduces the negative pattern of the mask with a resolution of 2 μm. The pEtOx₈₀Bu⁼Ox₂₀ ‐derived photoresists can also be developed in water.     

Nitroxide mediated synthesis of low dispersity random copolymers for low‐loss optical waveguides

Candidate materials for low‐loss optical waveguides based on poly(glycidyl methacrylate‐ran‐pentafluostyrene) [P(GMA‐ran‐PFS)] copolymers were synthesized by nitroxide mediated polymerization (NMP) initiated with BlocBuilder^® [N‐(2‐methylpropyl)‐N‐(1‐diethlphosphono‐2,2‐dimethylpropyl)‐O‐(2‐carboxylprop‐2‐yl) hydroxylamine] bearing a succinimidyl ester group (NHS‐BlocBuilder) at 90 °C in 1,4 dioxane. The copolymerizations yielded copolymers with low dispersity M_w/M_n between 1.2 and 1.4. The core structure of single‐mode channel waveguides was fabricated by direct UV lithographic patterning. The copolymers with low M_w/M_n resulted in line width roughness (LWR) of about 0.16 μm, whereas LWR of copolymers with M_w/M_n=3.5 but similar compositions was about 0.5 μm. The improvement in microstructural control allotted by NMP permitted finer pattern replication for copolymers desired for optical waveguides, as suggested for photoresist polymers. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2970–2978     

Development of a simple HPLC–MS/MS method to simultaneously determine teriflunomide and its metabolite in human plasma and urine: Application to clinical pharmacokinetic study of teriflunomide sodium and leflunomide

A simple high‐performance liquid chromatography coupled with tandem mass spectrometry method was developed and fully validated to simultaneously determine teriflunomide (TER) and its metabolite 4‐trifluoro‐methylaniline oxanilic acid (4‐TMOA) in human plasma and urine. Merely 50 μL plasma and 20 μL urine were employed in sample preparation using protein precipitation and direct dilution method, respectively. An Agilent Zorbax eclipse plus C₁₈ column was selected to achieve rapid separation for TER and 4‐TMOA within 3 min. Electrospray ionization under multiple reaction monitoring was used to monitor the ion transitions for TER (m/z 269.0 → 159.9), 4‐TMOA (m/z 231.9 → 160.0), internal standard teriflunomide‐d4 (m/z 273.0 → 164.0) and 2‐amino‐4‐trifluoromethyl benzoic acid (m/z 203.8 → 120.1), operating in the negative ion mode. This method proved to have better accuracy and precision over concentration range of 10–5000 ng/mL in plasma as well as 10–10,000 ng/mL in urine. After a full validation, this method was successfully applied in a pharmacokinetic study of teriflunomide sodium and leflunomide in Chinese healthy volunteers.     

Simultaneous quantification of imatinib and its main metabolite N‐demethyl‐imatinib in human plasma by liquid chromatography–tandem mass spectrometry and its application to therapeutic drug monitoring in patients with gastrointestinal stromal tumor

The aim of this study was to improve and validate a more stable and less time‐consuming method based on liquid chromatography and tandem mass spectrometry (LC‐ MS/MS) for the quantitative measurement of imatinib and its metabolite N‐ demethyl‐imatinib (NDI) in human plasma. Separation of analytes was performed on a Waters XTerra RP₁₈ column (50 × 2.1 mm i.d., 3.5 μm) with a mobile phase consisting of methanol–acetonitrile–water (65:20:15, v /v/v) with 0.05% formic acid at a flow‐rate of 0.2 mL/min. The Quattro MicroTM triple quadruple mass spectrometer was operated in the multiple‐reaction‐monitoring mode via positive electrospray ionization interface using the transitions m /z 494.0 → 394.0 for imatinib, m /z 479.6 → 394.0 for NDI and m /z 488.2 → 394.0 for IS. The method was linear over 0.01–10 μg/mL for imatinib and NDI. The intra‐ and inter‐day precisions were all <15% in terms of relative standard deviation, and the accuracy was within ±15% in terms of relative error for both imatinib and NDI. The lower limit of quantification was identifiable and reproducible at 10 ng/mL. The method was sensitive, specific and less time‐consuming and it was successfully applied in gastrointestinal stromal tumor patients treated with imatinib.     

Inhibitors of the Bifunctional 2‐C‐Methyl‐d‐erythritol 4‐Phosphate Cytidylyl Transferase/2‐C‐Methyl‐d‐erythritol‐2,4‐cyclopyrophosphate Synthase (IspDF) of Helicobacter pylori

A library of over 103 thousand compounds was screened for inhibitors of the IspD domain (2‐C‐methyl‐d ‐erythritol 4‐phosphate cytidylyl transferase domain) of the bifunctional IspDF protein from Helicobacter pylori using a photometric assay. Around 300 compounds showed IC₅₀ values below 100 μm , and three compounds had IC₅₀ values below 1 μm . A few IspD inhibitors could also inhibit the IspF domain (2‐C‐Methyl‐d ‐erythritol‐2,4‐cyclopyrophosphate synthase) of the IspDF protein. The most potent IspD inhibitors were tested as growth inhibitors of H. pylori. Several compounds showed inhibition of bacterial growth with IC₅₀ in the single‐digit μm range. The most potent growth inhibitor had an IC₅₀ value of 3.4 μm . The most potent growth inhibitor without measurable effect on eukaryotic cell viability had an IC₅₀ value of 7.2 μm .     

Evaluation of Enzymatic Kinetics of GOx‐based Electrodes by Scanning Electrochemical Microscopy at Redox Competition Mode

Glucose oxidase (GOx) is an enzyme, which is used for the development of enzymatic biofuel cells. Therefore in this research redox competition mode of scanning electrochemical microscopy (RC‐SECM) was applied for the investigation of glucose oxidase (GOx) catalyzed reaction kinetics. The GOx was immobilized by glutaraldehyde on substrates of different electrical conductivity: (i) gold covered glass was used as conducting substrate and (ii) plastic poly(methyl methacrylate) was used as non‐conducting substrate. Current vs distance dependencies were registered by SECM at different concentrations of glucose in the absence of redox mediator. The potential of −750 mV vs Ag/AgCl(3 M KCl) was applied to the microelectrode (ME), which was used as a probe in SECM, in order to register oxygen reduction current. Consumption of oxygen by the GOx based layer was evaluated according to principles determined by Michaelis‐Menten kinetics. Apparent Michaelis constants K _{M (app.)} were calculated from the dependencies of current vs glucose concentration. In both these cases the K _{M (app.)} value increased when the distance between ME and enzyme modified surface was increasing from 10 to 30 μm, while the K _{M (app.)} value decreased by increasing the distance from 30 to 60 μm.     

Specific properties of in situ ruthenium‐catalyzed polyamide 12/polydimethylsiloxane compatibilized blend

The main objective of this work focused on the chemical modification of polyamide 12 (PA12) properties through the reaction with a hydride‐terminated polydimethylsiloxane (PDMS‐SiH). The investigated PA12/PDMS‐SiH blend was compatibilized by ruthenium derivative catalyzed hydrosilylation reaction in molten state. This original route enhanced interfacial adhesion and avoid PDMS‐SiH leaching phenomenon between the two immiscible phases. More specifically, the size of PDMS‐SiH domains in the blend decreased from around 4 μm to 800 nm and from 30 to 1 μm after compatibilization with 10 and 20 wt % PDMS‐SiH, respectively. For the best compatibilized PA12/PDMS‐SiH blend, the introduction of PDMS lowered the surface free energy and the PA12‐based blend turned from hydrophilic to hydrophobic behavior, as evidenced by the water contact angle measurements. Gas permeability and CO₂/H₂ and CO₂/He gas selectivity were also improved with the increase in PDMS content. Besides, the mechanical properties were enhanced with 13% increase in Young's modulus after in situ compatibilization with 15 wt % PDMS‐SiH. Thermal stability was also improved after compatibilization as the initial degradation temperature of reactive blends obviously increased compared with nonreactive ones. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 978–988     

Lithographic design of photosensitive polyarylates based on reaction development patterning

The factors affecting pattern‐forming properties in reaction development patterning were examined with polyarylates with various bisphenol moieties. The developability of the photosensitive polyarylates was dependent on the properties of the subtituent (R) in the bisphenol moieties. The development time decreased in the following order: R?C(CH₃)₂ > fluorenyl unit ? phenolphthalein unit > C(CF₃)₂ > SO₂. This order agreed with that of the reactivity between the polyarylates and ethanolamine, and these orders can be explained by pK_a of the bisphenol used to prepare the polyarylates. The development with NH₂? R′? OH resulted in successful positive‐tone pattern formation. However, pattern formation with the developers containing NH₂? R′? OCH₃ was unsuccessful. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 2694–2706, 2006     

A high‐throughput LC–MS/MS method for determination of flunarizine in human plasma: Pharmacokinetic study with different doses

A high‐throughput and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method has been developed and validated for the determination of flunarizine in human plasma. Liquid–liquid extraction under acidic conditions was used to extract flunarizine and flunarizine‐d8 from 100 μL human plasma. The mean extraction recovery obtained for flunarizine was 98.85% without compromising the sensitivity of the method. The chromatographic separation was performed on Hypersil Gold C₁₈ (50 × 2.1 mm, 3 μm) column using methanol–10 mm ammonium formate, pH 3.0 (90:10, v/v) as the mobile phase. A tandem mass spectrometer (API‐5500) equipped with an electrospray ionization source in the positive ion mode was used for detection of flunarizine. Multiple reaction monitoring was selected for quantitation using the transitions, m/z 405.2 → 203.2 for flunarizine and m/z 413.1 → 203.2 for flunarizine‐d8. The validated concentration range was established from 0.10 to 100 ng/mL. The accuracy (96.1–103.1%), intra‐batch and inter‐batch precision (CV ≤ 5.2%) were satisfactory and the drug was stable in human plasma under all tested conditions. The method was used to evaluate the pharmacokinetics of 5 and 10 mg flunarizine tablet formulation in 24 healthy subjects. The pharmacokinetic parameters C_max and AUC were dose‐proportional.     

Characterization of xylazine metabolism in rat liver microsomes using liquid chromatography–hybrid triple quadrupole–linear ion trap–mass spectrometry

ABSTRACT: Xylazine is an α₂‐adrenoceptor agonist and it is widely used in veterinary anesthesia in combination with ketamine. There is limited information on the metabolism of xylazine. A quantitative method for the determination of xylazine by HPLC‐ESI/MS/MS was developed. The method consisted of a protein precipitation extraction followed by analysis using liquid chromatography electrospray tandem mass spectrometry. The chromatographic separation was achieved using a Thermo Betasil Phenyl 100 × 2 mm column combined with an isocratic mobile phase composed of acetonitrile, methanol, water and formic acid (60:20:20:0.4) at a flow rate of 300 μL/min. The mass spectrometer was operating in selected reaction monitoring mode and the analytical range was set at 0.05–50 μm . The precision (%CV) and accuracy (%NOM) observed were 2.3–7.2 and 88.2–96.4%. In vitro metabolism studies were performed in rat liver microsomes and results showed moderate cytochrome P450 affinity (K_m = 10.1 μm ) and a low metabolic stability of xylazine with a half‐life of 4.1 min in rat liver microsomes. Five phase 1 metabolites were observed. The main metabolite observed was an oxidation of the thiazine moiety at m/z 235 and, to a lesser extent, we observed the formation of N‐(2,6‐dimethylphenyl)thiourea at m/z 181 and three distinctive hydroxylated metabolites at m/z 237. Further experiments with ketamine and ketoconazole strongly supported that the metabolism of xylazine to its main metabolite is mediated by CYP3A in rat liver microsomes. Copyright © 2013 John Wiley & Sons, Ltd.     

Gold‐Nanoparticle‐Loaded Carbonate‐Modified Titanium(IV) Oxide Surface: Visible‐Light‐Driven Formation of Hydrogen Peroxide from Oxygen

Gold nanoparticle‐loaded rutile TiO₂ with a bimodal size distribution around 10.6 nm and 2.3 nm (BM‐Au/TiO₂) was prepared by the deposition precipitation and chemical reduction (DP‐CR) technique. Visible‐light irradiation (λ>430 nm) of the BM‐Au/TiO₂ plasmonic photocatalyst yields 35 μm H₂O₂ in aerated pure water at irradiation time (t_p)=1 h, and the H₂O₂ concentration increases to 640±60 μm by the addition of 4 % HCOOH as a sacrificing electron donor. Further, a carbonate‐modified surface BM‐Au/TiO₂ (BM‐Au/TiO₂‐CO₃^2?) generates a millimolar level of H₂O₂ at t_p=1 h with a quantum efficiency (Φ) of 5.4 % at λ=530 nm under the same conditions. The recycle experiments confirmed the stable performance of BM‐Au/TiO₂.     

Simultaneous determination of sarpogrelate and its active metabolite in human plasma by liquid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study

We established a rapid and simple liquid chromatography with tandem mass spectrometry method for the simultaneous determination of sarpogrelate and its active metabolite, M‐1, in human plasma. Sarpogrelate, M‐1, and the internal standard, ketanserin, were extracted from a 50 μL aliquot of human plasma by protein precipitation using acetonitrile. Chromatographic separation was performed on a Shim‐pack GIS ODS C₁₈ column (100 × 3.0 mm; 3 μm) with an isocratic mobile phase consisting of 10 mM ammonium acetate and acetonitrile (70:30, v/v) at a flow rate of 0.6 mL/min; the total run time was <2.5 min. Mass spectrometric detection was conducted in selected reaction‐monitoring mode with positive electrospray ionization at m/z 430.35 → 135.10 for sarpogrelate, m/z 330.30 → 58.10 for M‐1, and m/z 395.70 → 188.85 for ketanserin. The linear ranges of concentration for sarpogrelate and M‐1 were 1–1000 and 0.5–500 ng/mL, respectively. The coefficient of variation for the assay's precision was ≤9.95%, and the accuracy was 90.6–107%. All analytes were stable under various storage and handling conditions, and no relevant crosstalk and matrix effect was observed. This method was successfully applied to a pharmacokinetic study after oral administration of a 100 mg sarpogrelate tablet to healthy male Korean volunteers.     

Characterization of in vitro metabolites of irisflorentin by rat liver microsomes using high‐performance liquid chromatography coupled with tandem mass spectrometry

Belamcanda chinensis has been extensively used as antibechic, expectorant and anti‐inflammatory agent in traditional medicine. Irisflorentin is one of the major active ingredients. However, little is known about the metabolism of irisflorentin so far. In this work, rat liver microsomes (RLMs) were used to investigate the metabolism of this compound for the first time. Seven metabolites were detected. Five of them were identified as 6,7‐dihydroxy‐5,3′,4′,5′‐tetramethoxy isoflavone (M1), irigenin (M2), 5,7,4′‐trihydroxy‐6,3′,5′‐trimethoxy isoflavone (M3), 6,7,4′‐trihydroxy‐5,3′,5′‐trimethoxy isoflavone (M4) and 6,7,5′‐trihydroxy‐5,3′,4′‐trimethoxy isoflavone (M5) by means of NMR and/or HPLC‐ESI‐MS. The structures of M6 and M7 were not elucidated because they produced no MS signals. The predominant metabolite M1 was noted to be a new compound. Interestingly, it was found to possess anticancer activity much higher than the parent compound. The enzymatic kinetic parameters of M1 revealed a sigmoidal profile, with V_max = 12.02 μm /mg protein/min, K_m = 37.24 μm , CL_int = 0.32 μL/mg protein/min and h = 1.48, indicating the positive cooperation. For the first time in this work, a new metabolite of irisflorentin was found to demonstrate a much higher biological activity than its parent compound, suggesting a new avenue for the development of drugs from B. chinensis, which was also applicable for other herbal plants. Copyright © 2016 John Wiley & Sons, Ltd.     

Effect of prepolymer molecular weight on solid state polymerization of poly(bisphenol a carbonate) with nitrogen as a sweep fluid

The effect of prepolymer molecular weight on the solid‐state polymerization (SSP) of poly(bisphenol A carbonate) was investigated using nitrogen (N₂) as a sweep fluid. Prepolymers with different number–average molecular weights, 3800 and 2400 g/mol, were synthesized using melt transesterification. SSP of the two prepolymers then was carried out at reaction temperatures in the range 120–190 °C, with a prepolymer particle size in the range 20–45 μm and a N₂ flow rate of 1600 mL/min. The glass transition temperature (T_g), number–average molecular weight (M_n), and percent crystallinity were measured at various times during each SSP. The phenyl‐to‐phenolic end‐group ratio of the prepolymers and the solid‐state synthesized polymers was determined using 125.76 MHz ¹³C and 500.13 MHz ¹H nuclear magnetic resonance (NMR) spectroscopy. At each reaction temperature, SSP of the higher‐molecular‐weight prepolymer (M_n = 3800 g/mol) always resulted in higher‐molecular‐weight polymers, compared with the polymers synthesized using the lower molecular weight prepolymer (M_n = 2400 g/mol). Both the crystallinity and the lamellar thickness of the polymers synthesized from the lower‐molecular‐weight prepolymer were significantly higher than for those synthesized from the higher‐molecular‐weight prepolymer. Higher crystallinity and lamellar thickness may lower the reaction rate by reducing chain‐end mobility, effectively reducing the rate constant for the reaction of end groups. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4959–4969, 2008     

In vitro ketamine CYP3A‐mediated metabolism study using mammalian liver S9 fractions,cDNA expressed enzymes and liquid chromatography tandem mass spectrometry

Ketamine is widely used in medicine in combination with several benzodiazepines, including midazolam. The objectives of this study were to develop a novel HPLC‐MS/selected reaction monitoring (SRM) method capable of quantifying ketamine and norketamine using an isotopic dilution strategy in biological matrices and study the formation of norketamine, the principal metabolite of ketamine with and without the presence of midazolam, a well‐known CYP3A substrate. The chromatographic separation was achieved using a Thermo Betasil Phenyl 100 × 2 mm column combined with an isocratic mobile phase composed of acetonitrile, methanol, water and formic acid (60:20:20:0.4) at a flow rate of 300 μL/min. The mass spectrometer was operating in selected reaction monitoring mode and the analytical range was set at 0.05–50 μm . The precision (CV) and accuracy (NOM) observed were 3.9–7.8 and 95.9–111.1% respectively. The initial rate of formation of norketamine was determined using various ketamine concentrations and K_m values of 18.4, 13.8 and 30.8 μm for rat, dog and human liver S9 fractions were observed, respectively. The metabolic stability of ketamine on liver S9 fractions was significantly higher in human (T_1/2 = 159.4 min) compared with rat (T_1/2 = 12.6 min) and dog (T_1/2 = 7.3 min) liver S9 fractions. Moreover significantly lower IC₅₀ and K_i values observed in human compared with rat and dog liver S9 fractions. Experiments with cDNA expressed CYP3A enzymes showed that the formation of norketamine is mediated by CYP3A but results suggest an important contribution from other isoenzymes, most likely CYP2C particularly in rat. Copyright © 2014 John Wiley & Sons, Ltd.     

Li2MnSnSe4: A New Quaternary Diamond‐Like Semiconductor with Nonlinear Optical Response and Antiferromagnetic Property

A new selenide with a diamond‐like structure, Li₂MnSnSe₄, was synthesized for the first time by using a conventional high‐temperature solid‐state reaction method. Li₂MnSnSe₄ crystallizes in the space group Pmn 2₁ (no. 31) of the orthorhombic system. Its three‐dimensional framework is constructed by corner‐sharing LiSe₄, MnSe₄, and SnSe₄ tetrahedra. The title compound has been discovered to have both type I phase‐matchable behavior and to exhibit moderate powder second‐harmonic generation intensity, about 0.5 times that of commercial AgGaS₂ in the particle size of 200–250 μm at a laser radiation of 2.09 μm. In addition, Li₂MnSnSe₄ exhibits congruent melting behavior, which makes the bulk single‐crystal growth by the Bridgman–Stockbarger method possible. The temperature‐dependent susceptibility measurement indicates an antiferromagnetic interaction with a Néel temperature (T _N) of 8.6 K for this compound.     

Quantification of β‐eudesmol in rat plasma using LC–MS/MS and its application to a pharmacokinetic study

A sensitive and specific LC–MS/MS assay for determination of β ‐eudesmol in rat plasma was developed and validated. After liquid–liquid extraction with ethyl ether , the analyte and IS were separated on a Capcell Pak C₁₈ column (50 × 2.0 mm, 5 μm) by isocratic elution with acetonitrile—water–formic acid (77.5:22.5:0.1, v /v/v) as the mobile phase at a flow rate of 0.4 mL/min. An ESI source was applied and operated in positive ion mode; a selected reaction monitoring scan was used for quantification by monitoring the precursor–product ion transitions of m/z 245.1 → 163.1 for β ‐eudesmol and m/z 273.4 → 81.2 for IS. Good linearity was observed in the concentration range of 3–900 ng/mL for β ‐eudesmol in rat plasma. Intra‐ and inter‐day precision and accuracy were both within ±14.3%. This method was applied for pharmacokinetic studies after intravenous bolus of 2.0 mg/kg or intragastric administration of 50 mg/kg β ‐eudesmol in rats.