Bromadiolone poisoning: LC-MS method and pharmacokinetic data

Abstract:  Poisoning with superwarfarins, like bromadiolone, is a growing public health problem, and the mortality is high. Pharmacokinetic data on bromadiolone in humans are however scarce, and there are no reports following repeated exposures to bromadiolone. We have developed a method for quantification of bromadiolone in whole blood, using liquid chromatography–mass spectrometry (LC-MS). The analytical method is reported. Limit of detection was 0.005 mg/L and limit of quantification was 0.01 mg/L. The concentrations of bromadiolone in whole blood and plasma in serial samples from a 62-year-old woman were measured. The half-life of bromadiolone in blood was estimated to be about 6 days in the initial phase of elimination and about 10–13 days in the terminal phase. The mean plasma/blood ratio of bromadiolone was 1.7 ± 0.6. Stability testing of bromadiolone in whole blood samples after two cycles of freeze and thaw revealed that bromadiolone concentrations decreased.     

LC-MS／MS测定尿液中可卡因及其代谢物苯甲酰爱康宁

目的建立尿液中可卡因(cocaine,COC)及其代谢物苯甲酰爱康宁(benzoylecgonine,BZE)的液相色谱-串联质谱分析方法。方法尿液经固相萃取后,用AllurePFP丙基柱分离,以V(甲醇):V(20mmol/L乙酸胺和0.1%甲酸的缓冲溶液)=80∶20为流动相,采用二级质谱多反应监测模式检测COC和BZE。按10mg/kg的剂量对豚鼠腹腔注射可卡因,给药后收集7d尿液。结果尿液中COC和BZE在2.0～100ng/mL质量浓度范围内线性关系良好(r=0.9995),最低检测限(LOD)为0.5ng/mL;回收率大于90%;日内和日间精密度均小于6%;豚鼠尿液中主要检测目标物是BZE,且BZE检测时限也较COC长。结论所建方法灵敏度高,选择性好,适用于尿液中可卡因和苯甲酰爱康宁的检测。     

Identification of colorants in pigmented pen inks by laser desorption mass spectrometry

Pigments are rapidly replacing dyes as colorants in pen and printer inks, due to their superior colors and stability. Unfortunately, tools commonly used in questioned document examination for analyzing pen inks, such as TLC, cannot be used for the analysis of insoluble pigments on paper. Laser desorption mass spectrometry is demonstrated here as a tool for analyzing pigment-based pen inks. A pulsed nitrogen laser can be focused onto a pen stroke from a pigmented ink pen on paper, and positive and negative ions representative of the pigment can be generated for subsequent mass spectrometric analysis. Targeted pens for this work were a set of Uni-ball 207 pigmented ink pens containing blue, light blue, orange, green, violet, red, pink, and black inks. Copper phthalocyanine was identified as the pigment used to make both blue inks. A mixture of halogenated copper phthalocyanines were identified in the green ink. Unexpectedly, the pink ink was found to contain a red pigment, Pigment Red 12, treated with a mixture of water-soluble dyes. Each sample yielded ions representative of the pigments present.     

A solid-phase microextraction method for the detection of ignitable liquids in fire debris

A solid-phase microextraction (SPME) procedure involving direct contact between the SPME fibers and the solid matrix and subsequent gas chromatography/mass spectrometric analysis for the detection of accelerants in fire debris is described. The extraction performances of six fibers (100 mum polydimethylsiloxane, 65 mum polydimethylsiloxane-divinylbenzene, 85 mum polyacrylate, 85 mum carboxen-polydimethylsiloxane, 70 mum Carbowax-divinylbenzene, and 50/30 mum divinylbenzene-Carboxen-polydimethylsiloxane) were investigated by directly immersing the fibers into gasoline, kerosene, and diesel fuel. For simulated fire debris, in the direct contact extraction method, the SPME fiber was kept in contact with the fire debris matrix during extraction by penetrating plastic bags wrapping the sample. This method gave comparable results to the headspace SPME method in the extraction of gasoline and kerosene, and gave an improved recovery of low-volatile components in the extraction of diesel fuel from fire debris. The results demonstrate that this procedure is suitable as a simple and rapid screening method for detecting ignitable liquids in fire debris packed in plastic bags.     

Hair analysis to document non-fatal pesticide intoxication cases

We reported two non-fatal cases of intoxication with pesticides namely alachlor and carbofuran. Hair stand samples were collected from two men approximately 1 year after alachlor intoxication for case 1, and 14 days after the last exposure for case 2. Hair analysis was performed using a liquid chromatography-tandem mass spectrometry method. In case 1, alachlor was detected in the 5 analysed hair segments (concentrations between 12 and 136 pg/mg) and its metabolites were not detected. In case 2, carbofuran and its main metabolite (3-hydroxycarbofuran) were detected in the hair strand (global analysis) at the concentrations of 207 and 164 pg/mg, respectively. However, additional data are required in order to interpret such results.     

Application of discriminant analysis to differentiate between incorporation of cocaine and its congeners into hair and contamination

The requirement to differentiate between incorporation and external contamination of drugs into hair is undisputed, in particular when dealing with compounds which are administered by sniffing or inhalation (e.g. cocaine). With the aim of making this discrimination, hair samples from cocaine (COC) users (group IN) and seized cocaine samples (group OUT) were compared regarding the parameters benzoylecgonine (BZE), ecgonine methyl ester (EME), ecgonine (ECG), anhydroecgonine methyl ester (AEME), cocaethylene (CE) and norcocaine (NCOC). Since most of these compounds may be minor by-products of COC or be formed by biotransformation or chemical degradation, the stability of each substance was carefully examined. COC was found to be converted into significant amounts of BZE, EME and ECG even under mild extraction conditions, while traces of NCOC proved to be a ubiquitous by-product of COC. Cocaine positive hairs and seized cocaine samples (diluted to relevant concentrations) were equally preprocessed and analyzed by LC-MS-MS. Out of the metabolites listed above, NCOC, CE and AEME (each normalised to COC) were significantly increased in the incorporation group (i.e. hair samples from cocaine users). Based on this approach, a statistical discriminant analysis enabled us to make a prediction (and estimation of uncertainty) for each cocaine positive hair sample as to its likelihood of belonging to the group of cocaine users or of being contaminated.     

公司共同决策法律制度研究——以“职工满意度”为视角

职工参与共同决策是公司资本民主化和管理民主化的主要实现途径,起源于德国共同体文化的这一制度旨在保护职工权益、协调企业中劳资关系.寻找两者利益的平衡点,通过对不同企业的探索性调研,借助职工满意评价工具分析共同决策制度实施与职工满意之间的联系,探索我国公司法共同决策制度的引入模式.     

揭开集合侵权的面纱——从术语翻译到制度建构的追问

Masstort应译为“集合侵权”。“大规模侵权”存在形式和实质上之不足,不能标识恰当的判断标准,无法揭示整体性侵害这一本质,也难以统摄两大基本类型。基于整体结构转型、构成技术和归责机制失灵等原因,集合侵权不能融入传统侵权法,属于侵权法上的“情势变更”。为应对集合侵权,实体法须采取拟制集合团体、醇化责任基础、损害赔偿模型化、缓和证明责任等措施;同时,应以集团诉讼为中心构建程序制度,并实现私人自治和国家强制的结合。我国初步具备了应对集合侵权的实体法基础;程序法上还亟待建立集团诉讼制度,改变行政主导应对程序的现状。     

旅游让生活更美好？

随着旅游业的进一步发展和影响力的日益扩大,旅游的社会功能愈来愈受到学界关注。本文通过构建服务评估变量（服务公平性、服务质量、感知价值）、旅游满意和生活满意之间关系的整合模型,实证检验服务评估变量与旅游满意、生活满意之间的关系,验证旅游的社会贡献。通过抽样调查获取基础数据,采用结构方程模型（SEM）方法进行实证分析,发现服务评估变量的服务公平性对生活满意产生直接和间接影响,服务质量和感知价值通过旅游满意对生活满意产生间接影响,从而说明旅游地通过提供优质的旅游服务,能让人们生活更美好,进而实证验证了旅游的社会功能。文章最后指出研究局限和未来研究方向。