Conformation and internal mobility of 5H-dibenzo[a,d]cycloheptene derivatives in solution. Conformational analysis of highly flexible structures,part II

Summary The conformational possibilities of 5-(3-N,N-dimethylaminopropyl)-5H-dibenzo[a,d]cycloheptene (1), 5-(3-N,N-dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (2), and 5-(3-N,N-dimethylaminopropyl)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (3) are analysed using empirical force field methods. Minimum energy conformations, interconversion pathways, interconversion graphs and interconversion energies are examined in view of the analysis of conformer equilibria of1,2, or3 in solution. In addition, some basic requirements of the analysis of fast interconverting conformers using the lanthanide induced shift method are discussed.

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Konformation und interne Beweglichkeit von 5H-Dibenzo[a,d]cyclohepten Derivaten in Lösung. Konformationsanalyse hochflexibler Strukturen, Teil 2

Zusammenfassung Die konformativen Möglichkeiten von 5-(3-N,N-dimethylaminopropyl)-5H-dibenzo[a,d]cyclohepten (1), 5-(3-N,N-dimethylaminopropylidene)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten (2) und 5-(3-N,N-dimethylaminopropyl)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten (3) wurden mit Hilfe empirischer Kraftfeldmethoden analysiert. Jene Konformationen, die einem energetischen Minimum entsprechen, sowie Interkonversionswege, Interkonversionsgraphen und Interkonversionsenergien wurden in Hinblick auf die Analyse der Konformerengleichgewichte von1,2 oder3 in Lösung untersucht. Weiters werden noch einige grundlegende Voraussetzungen für die Analyse von sich schnell ineinander umwandelnden Konformeren mittels der Lanthaniden-induzierten Verschiebungsmethode besprochen.

     

牛血清蛋白对手性物质的毛细管电泳拆分

采用聚氧乙烯涂层毛细管柱，以牛血清蛋白(BSA)为手性添加剂，运用毛细管电泳电导检测对手性药物沙丁胺醇和多沙唑嗪以及DL-组氨酸、色氨酸、苏氨酸进行拆分。考察了涂层柱的稳定性和重现性。对影响手性分离的主要因素：缓冲溶液的浓度和酸度、BSA的浓度、有机溶剂的种类和浓度以及分离电压进行了系统的研究。结果表明：在选择的最佳实验条件下，各对映异构体在22min内得到基线分离。     

Fast simultaneous determination of 23 veterinary drug residues in fish,poultry, and red meat by liquid chromatography/tandem mass spectrometry

The misuses of veterinary drugs can result in the accumulation of residues in food of animal origin that can make its way to the final consumer. Herein we describe a simple method for the accurate determination of beta-lactams, quinolones, sulphonamides, and tetracyclines in fish, poultry, and red meat. No extraction cartridges were used; instead, the extraction process consisted of the addition of an organic solvents, shaking, centrifugation, and dilution. An extensive validation process demonstrated an excellent linearity (R² ≥ 0.99) for 23-drug residues. The recovery of drugs in different matrices at two concentration levels (n = 6) was in the range of 82–119%. The method was proved to be repeatable and reproducible with intra/inter-day measurements (RSDs lower than 20%). The quantification limits of drug residues were in the range of 0.8 to 45.3 ug/kg, which is well below the maximum residue limits set by most regulatory authorities. This method was successfully applied to the routine analysis of 20 fish, poultry, and red meat samples (n = 60).     

Application of capillary electrophoresis with different sample stacking strategies for the determination of a group of nonsteroidal anti-inflammatory drugs in the low microg x L(-1) concentration range

Several on-column sample preconcentration modes--large-volume sample stacking using the EOF pump (LVSEP), LVSEP with anion-selective exhaustive injection (LVSEP-ASEI) and field-amplified sample injection with sample matrix removal using the electroosmotic flow (EOF) pump (FAEP)--were used to analyze some nonsteroidal anti-inflammatory drugs (NSAIDs) by capillary electrophoresis, and then compared. Methanol was the background electrolyte solvent to suppress the EOF. The effect of the type and length of the solvent plug, and the sample injection time were investigated in FAEP to determine the conditions that provided the best response. LVSEP, LVSEP-ASEI, and FAEP improved the sensitivity of the peak area by 100-, 1200-, and 1800-fold, respectively. The methodology developed, in combination with solid-phase extraction (SPE), was applied to the analysis of water samples.     

Evaluation of micellar liquid chromatography and capillary zone electrophoresis for dope control in sport

Micellar liquid chromatography (MLC) and capillary zone electrophoresis (CZE) have been evaluated for the analysis of twelve banned drugs in sport including diuretics and -blockers. In MLC, a sodium dodecylsulphate aqueous solution has been used as mobile phase using an octadecylsilica column. In CZE, a pH 8 buffer solution and a silica capillary have been employed. Parameters of retention and efficiency have been compared. Limits of detection with UV detection at 254 nm and relative standard deviations for atenolol, furosemide, nadolol, spironolactone and triamterene were established and compared in both techniques. Examples of direct urine injection into the separation systems are presented. Drugs overlapping in MLC are well resolved in CZE, while the opposite is true for a limited number of drugs. Some interferences from urine may arise in CZE. The selectivity of analysis would be greatly enhanced by using both techniques, which require only filtration as pre-treatment.     

Prediction of aqueous solubility of drugs and pesticides with COSMO-RS

The COSMO-RS method, originally developed for the prediction of liquid-liquid and liquid-vapor equilibrium constants based on quantum chemical calculations, has been extended to solid compounds by addition of a heuristic expression for the Gibbs free energy of fusion. By this addition, COSMO-RS is now capable of a priori prediction of aqueous solubilities of a wide range of typical neutral drug and pesticide compounds. Only three parameters in the heuristic expression have been fitted on a data set of 150 drug-like compounds. On these data an rms deviation of 0.66 log-units was achieved. Later, the model was tested on a set of 107 pesticides, which have been critically selected based on two experimental data sources and by a crosscheck with an independent HQSAR model. On this data set an rms of 0.61 log-units was achieved, without any adjustments to the structurally extremely diverse pesticides. This result verifies the ability of this extended COSMO-RS to predict aqueous solubilities of drugs and pesticides of almost arbitrary structural classes. The new method is COSMO-RSol.     

安眠镇静药物的串联质谱分析方法

气相色谱以及气相色谱／质谱联用经常被用来分析生物体液样品中的药物。用这些方法分析时，需要在色谱分析前，进行长时间的样品制备和衍生化过程。本文描述了用地识别１６安眠镇静药物的ＥＩ／ＭＳ／ＭＳ过程，并且对两例服毒自杀者的尿样进行了检测。     

信息型常见毒物质谱用户库的建立及其在毒物快速筛选上的应用研究

质谱定性是目前世界上最通用的定性分析方法之一,在法庭科学领域毒物分析实践中,质谱一直是对未知样品进行药毒物筛选检测的利器.     

固定pH滴定法测定弱酸弱碱性药物

报道一种水溶液吕测定弱酸弱碱性药物的新型滴定分析方法－固定ｐＨ滴定法，其理论基础是弱酸弱碱在水溶液中各种存在形式的分布系数在ｐＨ值固定时为常数，对甲硝唑，盐酸美西律等离散常数在１０＾－８至１０＾－１１范围内的７种弱酸弱碱性药物进行测定。结果与药典法吻合，回收率在９９．４％～１００．６％，方法简便，快速，准确，制剂中的赋形剂及色物不影响测定。     

Polyelectrolyte microcapsules templated on poly(styrene sulfonate)-doped CaCO3 particles for loading and sustained release of daunorubicin and doxorubicin

A strategy to incorporate and release anti-cancer drugs of daunorubicin (DNR) and doxorubicin (DOX) in preformed microcapsules is introduced, which is based on charge interaction mechanism. Oppositely charged poly(allylamine hydrochloride) (PAH) and poly(styrene sulfonate) (PSS) were assembled onto PSS doped-CaCO₃ colloidal particles in a layer-by-layer manner to yield core-shell particles. After removal of the carbonate cores, hollow microcapsules with entrapped PSS were fabricated, which showed spontaneous loading ability of positively charged DNR and DOX. The drug loading was confirmed quantitatively by observations under confocal laser scanning microscopy, transmission electron microscopy and scanning force microscopy. Quantification of the drug loading was performed under different conditions, revealing that a larger amount of drugs could be incorporated at higher drug feeding concentrations and higher salt concentrations. However, putting additional polyelectrolyte layers on the microcapsules after core removal resulted in weaker drug loading efficiency. The drug release behaviors from the microcapsules with different layer numbers were studied too, revealing a diffusion controlled release mechanism at the initial stage (4 h).