几种中药材的化学成分及其定性定量检测方法研究

本论文由四部分组成。第一部分报道了佛手参提取物的化学成分研究，建立了活性成分含量测定的高效液相测定和指纹图谱研究，采用液质联用技术鉴定了主要色谱峰；第二部分报道了丹参及其复方制剂的特征图谱研究；第三部分探讨了两面针生物碱的电喷雾质谱裂解规律，并采用液质联用技术分离鉴定了提取物中的多种生物碱。第四部分概述了液质联用在药物代谢研究中的运用。 第一部分包括第一、第二和第三章。第一章针对佛手参（Gymnadeniaconopsea）块茎的甲醇提取物，采用大孔树脂和反相硅胶柱层析等各种分离方法，共分离鉴定出4 个化合物，通过波谱分析将它们的结构确定为dactylorhin B (1)、loroglossin (2)、dactylorhin A (3)和militarine (4)。这4 个化合物均是首次从佛手参中分离得到的琥珀酸葡萄糖苷类成分。第二章采用高效液相色谱法对西藏、四川、河北、青海和尼泊尔等不同地区产的十个佛手参样品进行腺嘌呤核苷和对羟基苯甲醇的定量分析，结果表明这2 个成份可视为佛手参的特征成分，但也注意到产地不同该2 个特征成分的含量也有所不同。第三章采用标准中药指纹图谱相似度计算软件，以10 个佛手参样品HPLC 图谱的平均值为相似性评价对照模板，对10 个样品进行了相似度评价，并经液质联用分析指认了7 个共有峰，分别为腺嘌呤核苷(1)、对羟基苯甲醇(2)、对羟基苯甲醛(3) 、dactylorhin B(4) 、loroglossin(5)、dactylorhin A(6)和militarine(7)。 第二部分包括第四、第五、第六和第七章。第四章运用电喷雾质谱检测了对照药材和五个不同产地的丹参药材中脂溶性和水溶性成分，系统地探讨了多种成分的电喷雾质谱规律，并以对照药材为标准建立了特征指纹图谱。五个产地的药II材通过与对照药材相对比，采用聚类分析的方法，得到了定性的鉴别与判断。并采用液质联用技术对丹参药材提取液中的化学成份进行分析，推测了九个特征峰，并对六样品的液相色谱图进行了聚类分析。第五章探讨了三七皂苷的电喷雾质谱电离和裂解规律，并采用电喷雾质谱法对三七标准药材，血通片中的皂苷成分进行了分析。第六章运用电喷雾质谱研究复方丹参片提取液的特征图谱，并和单味药材丹参和三七的特征图谱进行了对比研究。并运用HPLC-ESI MSn 分析鉴定了复方丹参片提取液中的化学成分，推测了12 个色谱峰。第七章总结了电喷雾质谱和液质联用技术在丹参药材，三七药材及复方丹参制剂中的运用的优势和局限性。 第三部分（第八章）研究了两面针生物碱中二氢白屈菜红碱(1)、二氢两面针碱(2)、8-酮基二氢白屈菜红碱(3)、8-丙酮基二氢两面针碱(4)、两面针碱(5)、和1,3-二(8-二氢两面针碱)丙酮(6)等六个苯并菲啶型生物碱的电喷雾质谱裂解规律，其中二氢两面针碱和二氢白屈菜红碱，8-丙酮基二氢两面针碱和8-酮基二氢白屈菜红碱是两对二个甲氧基分别在C-9 和C-10，C-10 和C-11 的同分异构体。实验结果表明，在相同的碰撞能下，这类位置异构体的ESI MS2 质谱二级碎片离子的相对峰度存在很大差异，这可以用于区分该类同分异构体，采用液-质联用可以对两面针的总生物碱提取物中的这些同分异构体加于区分。同时在本实验采用的液相色谱条件下，多种生物碱得到较好的分离，通过和对照品的保留时间，紫外吸收光谱及电喷雾质谱图对照，鉴定了11 个主要色谱峰。 第四部分（第九章）对液质联用技术在药物代谢中的运用进行了综述。 This dissertation consisted of four sections. The first two sections elaborated thephytochemical investigation of the rhizomes Gymnadenia conopsea R. Br., methoddevelopment for rapid identifying and qutifying the chemical condtituent of thistibetant medicine, and the chemical fingerprint analysis of rhizomes of G. conopsea,Salviae miltiorrhiza and P. notoginseng. The third section studied the fragmentationmechanism of six alkaloids from Zanthoxylum nitidium and method development forrapid identifying varieties of alkaloids from the extract of this herbal medicine. Thefourth section reviewed HPLC- MS method in drug metabolism studies. The first section consisted of chapters 1, 2, 3. Chapter 1 elaborated the phytochemicalinvestigation of Gymnadenia conopsea R. Br. Four succinate derivative esters wereisolated from the methanol extract of the rhizomes of G. conopsea through repeatedcolumn chromatography on normal and reversed phase silica gel, their structures weredetermined by ESI-MS, 1D and 2D NMR evidence. They were firstly discoveredfrom this species. In chapter 2, a high-performance liquid chromatography.diodearray detection (HPLC-DAD) method has been firstly developed for quantitation oftwo characteristic constituents, adenosine and 4-hydroxybenzyl alcohol, from theextract of rhizomes of G. conopsea. All 10 samples of G. conopsea contained differentamount of adenosine and 4-hydroxybenzyl alcohol. Adenosine and the4-hydroxybenzyl alcohol can be applied in identification and quality control for theroots of G. conopsea. In chapter 3, a high-performance liquid chromatography.diodearray detection.tandem mass spectrometry (HPLC-DAD-MSn) method has been firstly developed for chemical fingerprint analysis of rhizomes of G. conopsea andrapid identification of major compounds in the fingerprints. Comparing the UV andMS spectra with those of authentic compounds, seven main peaks in the fingerprintswere identified as adenosine, 4-hydroxybenzyl alcohol, 4-hydroxybenzyl aldehyde,dactylorhin B, loroglossin, dactylorhin A and militarine. The Computer AidedSimilarity Evaluation System for Chromatographic Fingerprint of TraditionalChinese Medicine (CASES) was employed to evaluate the similarities of 10 samplesof the rhizomes of G. conopsea collected from Sichuan, Qinghai and Hebei provincesand Tibet autonomous region of China, and Nepal. These samples from differentsources had similar chemical fingerprints to each other. The second section consisted of chapters 4, 5, 6 and 7. In chapter 4，both thecharacteristic spectra of liposoluble tanshinones and aqueous-soluble salvianolic acidswere established by the electrospray ionization mass spectrometry (ESI MS)technique and the differences between standard and crude rhizomes of Salviaemiltiorrhiza Bge. from 5 sources were analyzed. The law of electrospray ion trap mass(ESI ITMS) of typical tanshinones and salvianolic acids is studied.The analysis of the chemical constituent of rhizomes of Salviae miltiorrhiza Bge. byliquid chromatography coupled with mass spectrum (LC/MS) technique wasestablished，and the distances among standard herb and crude herb from 5 sourceswere calculated by clustering analysis. According the DAD spectra and MS2 data，9tanshinones could be speculated. In chapter 5, the character spectra of total saponinsin P. notoginseng extracts were established by ESI ITMS and selective ion monitoring(SIM) technology. The law of notoginsenosides by ESI MS2 was studied. In chapter 6,the characteristic spectra of Compound Danshen Tablet established and compared byESI-MS and HPLC/DAD/MS, 6 known tanshinones and 3 saponins were speculated.In chapter 7, the advantage and disadvantage of the strategy, using the ESI ITMS andLC/MS techniques for study of characteristic spetra of danshen and Compound Danshen Tablet, were summerized. The third section (chapter 8) studied the fragmentation mechanism of six alkaloids,dihydronitidine, dihydrochelerythrine, 8-acetonyl dihydronitidine,8-acetonyldrochelerythrine, nitidine and 1,3-bis (8-dihydronitidinyl)-acetone, by ESIMSn. Tandem mass spectrometry experiments indicated that different substitutionsites of the methoxyl groups at C-9 and C-10 or at C-10 and C-11 determined thedifferent abundances of the MS2 fragmentation ions using the same collision energy.According to the different abundances of MS2 product ions, positional isomericbenzo[c] phenanthridine alkaloids can be differentiated. Moreover, ten constituents inthe crude alkaloids extract from the roots of Zanthoxylum nitidium were rapidlyidentified by high-performance liquid chromatography coupled with tandem massspectrometry (HPLC-MSn), through comparing the retention times and ESI MSn spectra with the authentic standards. The fourth section (chapter 9) is a review on HPLC-MS method development in drug metabolism studies.

Land use and water quality response in the northern region of Changxing County

In this paper, taking the northern region of Changxing County for example, with ammonia nitrogen as a pollution assessment index, we used an improved export coefficient method for estimate polluting load of non-point source pollution (NSP) and the social pollution survey data in the study area to estimate point source pollution. By comparing the total pollution output and the national surface water environmental quality standards find that the whole study area achieves the second water quality standard. However, Jiapu Township exceeds the water quality standards seriously because of the superfluous point source pollution. The water quality of other Townships is good. Further analysis showed that different types of land use and proportions in the northern region of Changxing County have a significant impact on the non-point source pollution, the general law is farmland contributes the largest share of the non-point source pollution output, followed by residential area and bare land, besides, with the increase in the proportion of forest and the decrease of farmland and residential area, the non-point source pollution reduces gradually. © 2010 IEEE.

Organizational excellence through quality governance

This paper provides an overview of an Enterprise Engineering method called IEM (Integrated Enterprise Modeling) and it describes the usage of SIX SIGMA approach for performance measurement of an enterprise. Based on these two instruments a methodology including procedure and tools is developed, which allows enterprises to define their adequate quality criteria for performance, to measure performance and quality and to derive reasonable actions to take for optimization. Determination of adequate quality and performance criteria and reasonable measures for the enterprise organization means “Quality Governance”.

Impacto de los factores interculturales en la implementación de un efectivo control de gestión en las organizaciones

Este trabajo pretende de una manera tanto teórica como práctica, estudiar la relación que pueda existir entre la interculturalidad y el Management Control System, para ello se realiza una revisión bibliográfica de los trabajos empíricos y teóricos desarrollados hasta el momento sobre el tema. Se comienza con la revisión de los diferentes conceptos que puedan hacer alusión a la interculturalidad, y los MCS (o contemple variables cercanas en relación a este), se delimita el tema y se procede a su clasificación hasta llegar a la estructuración de la definición de los constructos que integren los conceptos de interculturalidad y MCS. De igual manera, se operacionalizan las variables para poder generar un análisis practico utilizando estadística cuantitativa. Finalmente presentamos los resultados que demuestran el grado de importancia percibido por encuestados de filiales localizadas en diferentes países de Latino América de la empresa Agrocampo S.A.S, con el fin de presentar conclusiones que integren los dos temas de análisis.

Uma proposta para preparação de pequenas e médias empresas brasileiras prestadoras de serviços ao setor de telecomunicações para implantação da metodologia Seis Sigma

The objective of this work consists of considering a script so that operating companies in the telecommunications sector, mainly small and medium-sized enterprises, can reach excellency in its operations and get, thus, conditions to compete with companies consolidated in its niche of market. The proposal intends to lead the enterprises to a level of qualification of processes that to become them apt to adopt the Six Sigma method as part of its culture. From the analysis of the essential processes of the sector, methods and tools will be suggested for guarantee the continuous improvement of these processes, without forgetting the internal peculiarities of each company

Proposta de um modelo de gestão da qualidade para micro e pequenas empresas integrando a estratégia seis sigma à NBR ISO 9001

This work has as its main purpose to set a model of Quality Management for micro and small companies integrating the management models: Six Sigma strategy to NBR ISO 9001:2000. An exploratory research is developed to collect technical and bibliographical information on both methods, emphasizing their integration. Then, a survey is carried out on 65 analysts/consultants of Quality Management Systems and it has detected, besides other factors, that current methodologies must be associated in order to reach better results. At last, it proposes the Sigma 9001 model, which aims to make it possible for micro and small companies to objectively and with low costs, implement a Quality Management System, able to assure competitive advantage through improvement identification in the processes, as well as an improvement in the companies management

Qualidade em obras públicas: um estudo comparativo entre as metodologias Seis Sigma, ISO 9000 e PBQP-H no RN

In Brazil the theme quality in public construction has been widely discussed in the early 1990s, with the creation of the Brazilian Program of Quality and Productivity for the Habitat (PBQP-H) which is strongly influenced by the wave of studies on issues of quality in the world, such as the ISO 9000. Over the years, other approaches have emerged and been consolidated, evolving from market and customer´s needs. An example is the Six Sigma methodology. This study aims to examine the Six Sigma, ISO 9000 and PBQP-H methodologies, noting the common elements, differences, gaps and how the methods are complementary, so that with the ongoing work, proposed initiatives can be developed to improve the quality that enables its application in public construction. Still aiming to optimize the deployment of the proposed initiatives, it was performed an analysis of ISO 9001 and PBPQ-H certifications in Brazil and in the state of Rio Grande do Norte, with respect to the construction industry and a case study to identify the factors that influence the adoption of initiatives to improve quality, and check if the selected construction company is prepared to implement the proposed initiatives. This research is characterized as exploratory and applied, with literature review and a case study. The data collection instrument was a questionnaire and the statistical analysis used a multidimensional scaling method. The conclusion is that the methodologies are compatible and complementary, and their integration could potentialize the goals set. It was identified that the state of Rio Grande do Norte has a few number of certifications in construction. Nine initiatives are proposed for implementation at construction companies. In the case study it was found that the studied company would be able to implement the suggestions proposed and the requirement for certification by clients and funding institutions influence the adoption of quality improvement initiatives. This result confirms the literature which states that top management support is crucial for the successful implementation of quality methodologies

Seis sigma :uma proposta para implementação da metodologia em pequenas e médias empresas

The Six Sigma methodology consists of a program guided to the continuous improvement of enterprise processes, which aims at customer satisfaction, as well as increasing financial and operational profits. Considering that more than 99% of the Brazilian companies have up to five hundred employees, this study investigates how Six Sigma can be applied in small or medium size companies. This study was conducted based on literature review and application of the ideas in a medium size newspaper company, which manufactures newspapers that circulate daily in the state of Rio Grande do Norte. The results of the research point to the viability of use of the methodology in this market segment, as well as suggest a method that can be used in similar companies

Aplicação da abordagem estatística no contexto da gestão da qualidade: um survey b com indústrias de alimentos de São Paulo

Nas últimas duas décadas, o crescimento do interesse pela metodologia Seis Sigma intensificou a aplicação da abordagem estatística e de outras abordagens quantitativas com o intuito de melhorar não apenas a qualidade de produtos, serviços e processos, como também aumentar o desempenho organizacional e o processo de tomada de decisão. Este artigo trata da aplicação da abordagem estatística no contexto da gestão da qualidade em indústrias de alimentos de médio e grande porte do Estado de São Paulo com o propósito de: identificar quais ferramentas e técnicas estatísticas são mais amplamente empregadas por indústrias do setor para garantir e controlar a qualidade; avaliar a interdependência entre o sucesso da implementação de programas de qualidade e segurança alimentar como Boas Práticas de Fabricação (BPF) e sistema de Análise de Perigos e Pontos Críticos de Controle (APPCC) e o uso de estatística; e analisar estimativas do grau de relevância do pensamento estatístico e de seus benefícios como ferramenta de melhoria da qualidade. Um survey exploratório-descritivo foi realizado e os resultados revelaram que a abordagem estatística começa a ser mais valorizada nas indústrias de alimentos pela relevância de seus benefícios assim como já ocorre em outros setores. Há evidências de que a implantação bem sucedida dos programas de segurança alimentar seja uma condição primordial para o uso efetivo de estatística e de outras abordagens quantitativas.

Monitoring a wandering mean with an np chart

Este artigo considera um gráfico np x proposto por Wu et al. (2009) para controle de média de processo como uma alternativa ao uso do gráfico de. O que distingue do gráfico de controle np x é o fato das unidades amostrais serem classificadas como unidades de primeiro ou de segunda classe de acordo com seus limites discriminantes. O gráfico tradicional np é um caso particular do gráfico np x quando os limites discriminantes coincidem com os limites de especificação e unidade de primeira (segunda) classe é um item conforme (não conforme). Estendendo o trabalho de Reynolds Junior, Arnold e Baik (1996), consideramos que a média de processo oscila mesmo na ausência de alguma causa especial. As propriedades de Cadeia de Markov foram adotadas para avaliar o desempenho do gráfico np x no monitoramento de média de processos que oscila. de modo geral, o gráfico np x requer amostras duas vezes maior para superar desempenho do gráfico (enquanto que o gráfico tradicional np necessita tamanho de amostras cinco ou seis vezes maior).

Screening Brazilian automotive gasoline quality through quantification of saturated hydrocarbons and anhydrous ethanol by gas chromatography and exploratory data analysis

In this paper a set of Brazilian commercial gasoline representative samples from São Paulo State, selected by HCA, plus six samples obtained directly from refineries were analysed by a high-sensitive gas chromatographic (GC) method ASTM D6733. The levels of saturated hydrocarbons and anhydrous ethanol obtained by GC were correlated with the quality obtained from Brazilian Government Petroleum, Natural Gas and Biofuels Agency (ANP) specifications through exploratory analysis (HCA and PCA). This correlation showed that the GC method, together with HCA and PCA, could be employed as a screening technique to determine compliance with the prescribed legal standards of Brazilian gasoline.

Image quality evaluation of chest for computed radiography

The daily-to-day of medical practice is marked by a constant search for an accurate diagnosis and therapeutic assessment. For this purpose the doctor serves up a wide variety of imaging techniques, however, the methods using ionizing radiation still the most widely used because it is considered cheaper and above all very efficient when used with control and quality. The optimization of the risk-benefit ratio is considered a major breakthrough in relation to conventional radiology, though this is not the reality of computing and digital radiology, where Brazil has not established standards and protocols for this purpose. This work aims to optimize computational chest radiographs (anterior-posterior projection-AP). To achieve this objective were used a homogeneous phantoms that simulate the characteristics of absorption and scattering of radiation close to the chest of a patient standard. Another factor studied was the subjective evaluation of image quality, carried out by visual grading assessment (VGA) by specialists in radiology, using an anthropomorphic phantom to identify the best image for a particular pathology (fracture or pneumonia). Quantifying the corresponding images indicated by the radiologist was performed from the quantification of physical parameters (Detective Quantum Efficiency - DQE, Modulation Transfer Function - MTF and Noise Power Spectrum - NPS) using the software MatLab®. © 2013 Springer-Verlag.

Characterization of flavonoids and phenolic acids in Myrcia bella cambess. Using FIA-ESI-IT-MSn and HPLC-PAD-ESI-IT-MS combined with NMR

The leaves of Myrcia DC. ex Guill species are used in traditional medicine and are also exploited commercially as herbal drugs for the treatment of diabetes mellitus. The present work aimed to assess the qualitative and quantitative profiles of M. bella hydroalcoholic extract, due to these uses, since the existing legislation in Brazil determines that a standard method must be developed in order to be used for quality control of raw plant materials. The current study identified eleven known flavonoid-O-glycosides and six acylated flavonoid derivatives of myricetin and quercetin, together with two kaempferol glycosides and phenolic acids such as caffeic acid, ethil galate, gallic acid and quinic acid. In total, 24 constituents were characterized, by means of extensive preparative chromatographic analyses, along with MS and NMR techniques. An HPLC-PAD-ESI-ITMS and FIA-ESI-IT-MSn method were developed for rapid identification of acylated flavonoids, flavonoid-O- glycosides derivatives of myricetin and quercetin and phenolic acids in the hydroalcoholic M. bella leaves extract. The FIA-ESI-IT-MS techinique is a powerful tool for direct and rapid identification of the constituents after isolation and NMR characterization. Thus, it could be used as an initial method for identification of authentic samples concerning quality control of Myrcia spp extracts. © 2013 by the authors.

Estudo do efeito bake hardening nos aços BH 180 e BH 220 galvanizados pelo processo de imersão a quente

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Determination of pantoprazole in human plasma by LC-MS-MS using lansoprazole as internal standard

An analytical method based on liquid chromatography with positive ion electrospray ionization (ESI) coupled to tandem mass spectrometry detection was developed for the determination of pantoprazole (CAS 102625-70-7) in human plasma using lansoprazole (CAS 103577-45-3) as the internal standard. The analyte and internal standard were extracted from the plasma samples by liquid/liquid extraction using diethyl-ether/dichloromethane (70:30; v/v) and chromatographed on a C-8 analytical column. The mobile phase consisted of acetonitrile/water/methanol (57:25:18; v/v/v) + 10 mmol/l acetic acid + 20 mmol/l ammonium acetate. The method has a chromatographic total run time of 4.5 min and was linear within the range 5.0-5,000 ng/mL. Detection was performed on a triple quadrupole tandem mass spectrometer by Multiple Reaction Monitoring (MRM). The intra- and inter-run precisions calculated from quality control (QC) samples were 4.2% and 3.2%, respectively. The accuracies as determined from QC samples were -5.0% (intra-run) and 2.0% (inter-run). The method herein described was employed in a bioequivalence study of two tablet formulations of pantoprazole.