Concentration profiles of cocaine, pyrolytic methyl ecgonidine and thirteen metabolites in human blood and urine: determination by gas chromatography-mass spectrometry

When cocaine is smoked, a pyrolytic product, methyl ecgonidine (anhydroecgonine methyl ester), is also consumed with the cocaine. The amount of methyl ecgonidine formed depends on the pyrolytic conditions and composition of the illicit cocaine. This procedure describes detection of cocaine and 10 metabolites--cocaethylene, nor-cocaine, nor-cocaethylene, methyl ecgonine, ethyl ecgonine, benzoylecgonine, nor-benzoylecgonine, m-hydroxybenzoylecgonine, p-hydroxybenzoylecgonine and ecgonine--in blood and urine. In addition, the detection of pyrolytic methyl ecgonidine and three metabolites--ecgonidine (anhydroecgonine), ethyl ecgonidine (anhydroecgonine ethyl ester) and nor-ecgonidine (nor-anhydroecgonine)--are included. The newly described metabolites, ethyl ecgonidine and nor-ecgonidine, were synthesized and characterized by gas chromatography-mass spectrometry (GC-MS). All 15 compounds were extracted from 3 mL of blood or urine by solid-phase extraction and identified by a GC-MS method. The overall recoveries were 49% for methyl ecgonine, 35% for ethyl ecgonine, 29% for ecgonine and more than 83% for all other drugs. The limits of detection were between 0.5 and 4.0 ng/mL except for ecgonine, which was 16 ng/mL. Linearity for each analyte was established and in all cases correlation coefficients were 0.9985-1.0000. The procedure was applied to examine the concentration profiles of analytes of interest in post-mortem (PM) blood and urine, and in urine collected from living individuals (LV). These specimens previously were shown to be positive for the cocaine metabolite, benzoylecgonine. Ecgonidine, the major metabolite of methyl ecgonidine, was present in 77% of PM and 88% of the LV specimens, indicating smoking as the major route of cocaine administration. The new pyrolytic metabolites, ethyl ecgonidine and nor-ecgonidine, were present in smaller amounts. The urine concentrations of nor-ecgonidine were 0-163 ng/mL in LV and 0-75 ng/mL in PM specimens. Ethyl ecgonidine was found only in PM urine at concentrations 0-39 ng/mL. Ethanol-related cocaine metabolites, ethyl ecgonine or cocaethylene, were present in 69% of PM and 53% of cocaine-positive LV specimens, implying alcohol consumption with cocaine use. The four major metabolites of cocaine--benzoylecgonine, ecgonine, nor-benzoylecgonine and methyl ecgonine--constituted approximately 88 and 97% of all metabolites in PM and LV specimens, respectively. The concentrations of nor-cocaine and nor-cocaethylene were consistently the lowest of all cocaine metabolites. At benzoylecgonine concentrations below 100 ng/mL, ecgonine was present at the highest concentrations. In 20 urine specimens, benzoylecgonine and ecgonine median concentrations (range) were 54 (0-47) and 418 ng/mL (95-684), respectively. Therefore, detection of ecgonine is advantageous when benzoylecgonine concentrations are below 100 ng/mL.     

Chemical Bonding and Pressure‐Induced Change of the Electron Configuration of Ytterbium in β‐YbAgGa2

Single‐phase polycrystalline samples of the intermetallic compound β‐YbAgGa₂ were synthesized by inductive heating and subsequent annealing for eight weeks at 670 K. Magnetic properties were characterized by susceptibility measurements and indicated intermediate valence of ytterbium at ambient pressure. Angle‐dispersive X‐ray powder diffraction data of orthorhombic β‐YbAgGa₂ indicate stability of the phase in the investigated pressure range from 0.1 MPa (ambient pressure) to 19 GPa. The pressure‐induced volume decrease is accompanied by an increase of the effective valence from 2.17 at ambient conditions to 2.71 at 16 GPa as evaluated by X‐ray absorption spectroscopy at the Yb L_III threshold. Analysis of the chemical bonding in β‐YbAgGa₂ by integrating the electron density of the polyanion in basins as defined by the electron localization function results in an electron count Yb^2.7+[(Ag^0.2—)(Ga1(3b)^1.0—)(Ga2(4b)^1.5—)]. This finding is close to the expected values calculated by means of the Zintl rules and fits well the results of magnetic susceptibility measurements and XAS investigations.     

The chemical bond in polyphosphides: crystal structures, the electron localization function, and a new view of aromaticity in P4(2-) and P5(-)

The incongruent solvation of M(I)4P6 species (M(I) = K, Rb, Cs) in liquid ammonia leads to a broad variety of polyphosphides such as P7(3-), P11(3-), and the putatively aromatic P4(2-) and P5(-), which we investigated by using NMR spectroscopy and single-crystal X-ray structure analysis. The structures of Cs2P4 x 2 NH3, (K@[18]crown-6)3K3(P7)2 x 10 NH3, Rb3P7 x 7 NH3, and (Rb@[18]crown-6)3P7 x 6 NH3 are discussed and compared. The electron localization function ELF is used in a comparison of the chemical bonding of various phosphorus species. The variances of the basin populations provide a well-established measure for electron delocalization and therefore aromaticity. While comparable variance is calculated for P4(2-) and P5(-) it is observed in the lone pairs rather than in the basin populations of the bonds as in the prototypical aromatic hydrocarbons such as benzene or the cyclopentadienide anion. For this behavior, the term "lone pair aromaticity" is proposed.     

Modified Wave Particle Duality and Black Hole Physics

de Broglie relation is revisited, in consideration of a generalization of canonical commuting relation. The possible effects on particle's localization and black hole physics are also discussed, in a heuristic manner.     

Human Serum Amyloid a Impaired Structural Stability of High-Density Lipoproteins (HDL) and Apolipoprotein (Apo) A-I and Exacerbated Glycation Susceptibility of ApoA-I and HDL

Human serum amyloid A (SAA) is an exchangeable apolipoprotein (apo) in high-density lipoprotein (HDL) that influences HDL quality and functionality, particularly in the acute phase of inflammation. On the other hand, the structural and functional correlations of HDL containing SAA and apoA-I have not been reported. The current study was designed to compare the change in HDL quality with increasing SAA content in the lipid-free and lipid-bound states in reconstituted HDL (rHDL). The expressed recombinant human SAA1 (13 kDa) was purified to at least 98% and characterized in the lipid-free and lipid-bound states with apoA-I. The dimyristoyl phosphatidylcholine (DMPC) binding ability of apoA-I was impaired severely by the addition of SAA, while SAA alone could not bind with DMPC. The recombinant human SAA1 was incorporated into the rHDL (molar ratio 95:5:1, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC): cholesterol: apoA-I) with various apoA-I:SAA molar ratios from 1:0 to 1:0.5, 1:1 and 1:2. With increasing SAA1 content, the rHDL particle size was reduced from 98 Å to 93 Å, and the α-helicity of apoA-I:SAA was decreased from 73% to 40% for (1:0) and (1:2), respectively. The wavelength maximum fluorescence (WMF) of tryptophan in rHDL was red-shifted from 339 nm to 345 nm for (1:0) and (1:2) of apoA-I:SAA, respectively, indicating that the addition of SAA to rHDL destabilized the secondary structure of apoA-I. Upon denaturation by urea treatment from 0 M to 8 M, SAA showed only a 3 nm red-shift in WMF, while apoA-I showed a 16 nm red-shift in WMF, indicating that SAA is resistant to denaturation and apoA-I had higher conformational flexibility than SAA. The glycation reaction of apoA-I in the presence of fructose was accelerated up to 1.8-fold by adding SAA in a dose-dependent manner than that of apoA-I alone. In conclusion, the incorporation of SAA in rHDL impaired the structural stability of apoA-I and exacerbated glycation of HDL and apoA-I.     

浊点萃取-高效液相色谱法同时测定人尿中的4种抗凝血鼠药

建立了基于浊点萃取同时测定人尿中杀鼠灵、杀鼠醚、溴敌隆和溴鼠灵的反相高效液相色谱法。以非离子表面活性剂TritonX-114为萃取剂,考察了色谱测定条件,优化了浊点萃取参数。5mL尿样中加入0.030gNaCl,30μL甲酸和5%(w/v)TritonX-114400μL,50℃萃取15min,4种目标物的萃取效率能达到85%以上。在选择的色谱条件下,以V(甲醇)∶V(1%甲酸)=90∶10为流动相,待测组分经反相C18色谱柱分离,于306nm波长处用二极管阵列检测器检测,10min可完成分析。4种鼠药中杀鼠醚在0.01～5.0mg/L,其余3种在0.02～5.0mg/L范围内呈良好的线性关系(r≥0.997);尿样的标准加入回收率为71.2%～114.5%;相对标准偏差小于7.0%。对于5mL尿液,富集相用50μL甲醇稀释,萃取浓缩因子可达到28倍。定量检出浓度分别为:杀鼠灵0.016mg/L,杀鼠醚0.001mg/L,溴敌隆0.005mg/L,溴鼠灵0.003mg/L。本法简便快速、灵敏可靠、绿色环保,能满足鼠药中毒应急检测的要求。     

高效液相色谱-串联质谱联用测定人血液中的全氟化合物

采用HPLC-ESI-MS/MS联用技术,建立了分析血样中9种全氟化合物(PFCs)的方法.以13C4标记的PFOS (MPFOS)作为内标物.以C18反相柱为分析柱,甲醇、醋酸铵为梯度洗脱淋洗液,9种分析物包括全氟己烷磺酸(PFHxS)、全氟庚酸(PFHpA)、全氟辛酸 (PFOA)、全氟辛烷磺酸(PFOS)、全氟壬酸(PFNA)、全氟癸酸(PFDA)、全氟十一酸(PFUnDA)、全氟十二酸(PFDoDA)和全氟十四酸(PFTA),在15 min内即可达到良好的分离.在血样前处理中,采用MTBE液-液萃取和固相萃取相结合的方法,进一步净化样品以延长色谱柱寿命;比较了4种固相萃取小柱对全氟化合物的萃取性能,最终选定HLB柱(Waters).本研究还讨论了两种C18反相柱Acclaim 120(50 mm×4.6 mm, 3 μm)和Acclaim120 (250 mm×4.6 mm, 5 μm)(Dionex) 对PFCs的分析性能,在本实验条件下,两种色谱柱具有相似的分离性能及检出限,线性范围在0.1～50 μg/L之间 (r≥0.9957);对于血液样品该方法的检出限在0.03～0.8 μg/L之间.本研究将该方法成功地应用于血样实际样品中全氟化合物的测定,加标回收除PFTA较低外,其它化合物均在74.2%～118.1%之间.     

In Vitro and In Vivo Human Body Odor Analysis Method Using GO:PANI/ZNRs/ZIF−8 Adsorbent Followed by GC/MS

Among various volatile organic compounds (VOCs) emitted from human skin, trans-2-nonenal, benzothiazole, hexyl salicylate, α-hexyl cinnamaldehyde, and isopropyl palmitate are key indicators associated with the degrees of aging. In our study, extraction and determination methods of human body odor are newly developed using headspace-in needle microextraction (HS-INME). The adsorbent was synthesized with graphene oxide:polyaniline/zinc nanorods/zeolitic imidazolate framework-8 (GO:PANI/ZNRs/ZIF−8). Then, a wire coated with the adsorbent was placed into the adsorption kit to be directly exposed to human skin as in vivo sampling and inserted into the needle so that it was able to be desorbed at the GC injector. The adsorption kit was made in-house with a 3D printer. For the in vitro method, the wire coated with the adsorbent was inserted into the needle and exposed to the headspace of the vial. When a cotton T-shirt containing body odor was transferred to a vial, the headspace of the vial was saturated with body odor VOCs. After volatile organic compounds were adsorbed in the dynamic mode, the needle was transferred to the injector for analysis of the volatile organic compounds by gas chromatography/mass spectrometry (GC/MS). The conditions of adsorbent fabrication and extraction for body odor compounds were optimized by response surface methodology (RSM). In conclusion, it was able to synthesize GO:PANI/ZNRs/ZIF−8 at the optimal condition and applicable to both in vivo and in vitro methods for body odor VOCs analysis.     

Green Tea (Camellia sinensis): A Review of Its Phytochemistry,Pharmacology, and Toxicology

Objectives Green tea (Camellia sinensis) is a kind of unfermented tea that retains the natural substance in fresh leaves to a great extent. It is regarded as the second most popular drink in the world besides water. In this paper, the phytochemistry, pharmacology, and toxicology of green tea are reviewed systematically and comprehensively. Key findings Green tea has been demonstrated to be good for human health. Nowadays, multiple pharmacologically active components have been isolated and identified from green tea, including tea polyphenols, alkaloids, amino acids, polysaccharides, and volatile components. Recent studies have demonstrated that green tea shows versatile pharmacological activities, such as antioxidant, anticancer, hypoglycemic, antibacterial, antiviral, and neuroprotective. Studies on the toxic effects of green tea extract and its main ingredients have also raised concerns including hepatotoxicity and DNA damage. Summary Green tea can be used to assist the treatment of diabetes, Alzheimer’s disease, oral cancer, and dermatitis. Consequently, green tea has shown promising practical prospects in health care and disease prevention.     

Identification of Human Dihydroorotate Dehydrogenase Inhibitor by a Pharmacophore-Based Virtual Screening Study

Human dihydroorotate dehydrogenase (hDHODH) is an enzyme belonging to a flavin mononucleotide (FMN)-dependent family involved in de novo pyrimidine biosynthesis, a key biological pathway for highly proliferating cancer cells and pathogens. In fact, hDHODH proved to be a promising therapeutic target for the treatment of acute myelogenous leukemia, multiple myeloma, and viral and bacterial infections; therefore, the identification of novel hDHODH ligands represents a hot topic in medicinal chemistry. In this work, we reported a virtual screening study for the identification of new promising hDHODH inhibitors. A pharmacophore-based approach combined with a consensus docking analysis and molecular dynamics simulations was applied to screen a large database of commercial compounds. The whole virtual screening protocol allowed for the identification of a novel compound that is endowed with promising inhibitory activity against hDHODH and is structurally different from known ligands. These results validated the reliability of the in silico workflow and provided a valuable starting point for hit-to-lead and future lead optimization studies aimed at the development of new potent hDHODH inhibitors.