Integrated quality by design (QbD) and design of experiments (DoE) approach for UFLC determination of telaprevir in rat serum

An ultrafast liquid chromatographic bioanalytical method was developed and validated for the determination of telaprevir in Wistar albino rat serum. Principles of quality by design (QbD) were implemented for enhancing the bioanalytical liquid–liquid extraction of telaprevir from rat serum. A Box–Behnken design was utilized in the studies by selecting extraction time, centrifugation speed, and vortex time as the critical method variables for evaluating their effect on the critical analytical attribute, i.e., %recovery of telaprevir. Chromatographic separation was achieved within a run time of 10?min using a C-18 column and mobile phase comprising of methanol:borate buffer of pH 9 (90:10 v/v) flowing at 1.2?mL/min. Photodiode array detection was performed at 270?nm. Results of validation studies were satisfactory. The method was linear over a concentration of 25–10,000?ng/mL. Limit of detection for the developed method was 10?ng/mL. Further, design of experiments (DoE) used for inter-day accuracy and precision study suggested superior method reliability. This integrated QbD- and DoE-based approach ensured the development of a validated and reliable analytical method for optimum bioanalysis of telaprevir in biological matrix.     

基于端点白化权函数聚类的水环境质量等级评价分析

为更准确地评价水环境质量,将端点三角白化权函数灰色评估引入到水质综合评价中.针对以往灰色白化权函数评估主要通过测定指标灰聚类系数判定被评价对象的优劣强弱等级进行等级识别评价,对三角白化权函数计算方法进一步扩展,完成多评价对象的准确等级定位及比较排序.将这种方法应用于山东省聊城市东昌湖水水质评价中,经实例计算证明基于三角白化权函数灰色评估评价模型的稳定性、合理性和实用性为水质评价研究方法提供了新的思路和借鉴.     

论双系统估计量的无偏性

人口普查质量评估中所使用的双系统估计量是否为无偏估计量是一个很值得深入讨论的问题。只有无偏,才能确保使用双系统估计量估计的目标总体实际人数及人口普查净误差平均等于它们的实际数。针对人口普查质量评估工作中所使用的双系统估计量,论证这个估计量的无偏性条件。采用从既定假设出发进行推演的路径论证。研究结果表明,双系统估计量是目标总体实际人数无偏估计量的必要但非充分的条件是,人口普查与其质量评估调查相互独立以及目标总体中的每一个人在人口普查中的登记概率相同,在质量评估调查中登记的概率也相同。     

中国国债期货与隐含择券期权定价

本文提出了一种双树拼接的改进BDT模型,在此基础上发展出两种方法为中国市场上的国债期货和择券期权定价。其中"直接定价法"直接使用双树拼接树图,"两步定价法"则是经期权调整的持有成本模型。对中国TF1403和T1603国债期货合约的实证研究表明,两种方法都是合理的,且各有优势,"两步定价法"与市场价格差异较小,"直接定价法"与市场价格同步性较高。     

Identification and quality evaluation of different processed products of Aconitum carmichaelii by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry and ultra-high-performance liquid chromatography-tandem mass spectrometry

Aconitum carmichaelii is widely used to treat chronic and intractable diseases due to its remarkable curative effect, but it is also a highly toxic herb with severe cardiac and neurotoxicity. It has been combined with honey for thousands of years to reduce toxicity and enhance efficacy, but there has been no study on the chemical constituent changes in the honey-processing so far. In this study, the chemical constituents of A. carmichaelii before and after honey-processing were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. The results showed that a total of 118 compounds were identified, of which six compounds disappeared and five compounds were newly produced after honey-processing, and the cleavage pathway of main components was elucidated. At the same time, 25 compounds were found to have significant effects on different products, among which four compounds with the biggest difference were selected for quantitative analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry. This study not only explained the chemical differences between the different products, but also helped to control the quality of the honey-processed products more effectively, and laid a foundation for further elucidating the mechanism of chemical constituent change during the honey-processing of A. carmichaelii.     

Qualitative identification and quantitative comparison of Physochlainae Radix from different regions based on chemometric methods

Physochlainae Radix (PR) is an essential herbal medicine that has been generally applied for treating cough and asthma. In this study, a comprehensive strategy for quality evaluation of PR from different origins was established by integrating qualitative identification, quantitative analysis, and chemometric methods. A total of 58 chemical components were identified by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS), and a sensitive and rapid UHPLC-QqQ-MS/MS method was established for the simultaneous determination of 12 compounds. In addition, multivariate statistical analysis was applied for discriminant analysis to compare the differences among 30 batches of PR samples. The results showed that the 30 batches of PR collected from four provinces could be clustered into three categories, in which scoparone, protocatechuic acid, tropic acid, and scopolin were important components to distinguish the primary and non-primary producing areas, as well as superior and inferior products of PR. Chemometric results were consistent and validated each other, and systematically explained the intrinsic quality characteristics of PR. This study first demonstrated that LC-MS combined with multivariate statistical analysis, provided a comprehensive and effective means for quality evaluation of PR.     

丹荷颗粒治疗高脂血症质量标志物发现研究

为寻找丹荷颗粒治疗高脂血症的质量标志物,该研究基于丹荷颗粒体内成分分析结果,采用Cytoscape软件构建高脂血症-共有靶点-丹荷颗粒体内成分作用网络,利用DAVID及String数据库分别对共有靶点进行生物过程、通路富集及网络拓扑分析,明确丹荷颗粒降脂作用关键靶点及成分,再建立油酸诱导的HepG2细胞脂质堆积模型验证关键成分的降脂药效,最后结合相关成分在制剂中的含量、稳定性、特征性综合确定质量标志物。结果发现,丹荷颗粒体内成分作用于CES1、ADORA2A、ADORA1、APOB、LDLR、PPARA、PPARG、INSR、ESR2、ESR1共10个高脂血症疾病靶点,主要参与脂质代谢过程以及PPAR、cAMP信号通路,其中LDLR、PPARA、PPARG可能是关键靶点,而网络中与关键靶点直接作用的成分为白藜芦醇、柚皮素。白藜芦醇和柚皮素均可降低油酸诱导的HepG2细胞内脂滴数量,改善细胞脂质堆积严重程度,并显著降低细胞内甘油三酯含量,可能为关键成分;鉴于入体成分白藜芦醇和柚皮素来源于制剂中虎杖苷及柚皮苷,且制剂中虎杖苷及柚皮苷特征明显、含量丰富、稳定,故虎杖苷及柚皮苷可作为丹荷颗粒治疗高脂血症的质量标志物。该研究为丹荷颗粒质量标准的建立提供了合理的候选质控指标。     

以史为鉴——化学科普中的人文素养教育

中国古代历史中蕴含着丰富的化学史资源,对这些资源的挖掘、解读,形成化学科普题材,既是化学教育的需要,也是加强思想政治教育背景下课程思政的现实要求。以寒食散为例,探讨中国古代化学史资源所蕴含的人文素养教育价值,认为化学科普中汲取历史资源,不仅增加了科普的趣味性,有利于向公众普及化学知识,还有助于公众树立正确的世界观和价值观。     

Evaluation of Physiological Characteristics,Soluble Sugars,Organic Acids and Volatile Compounds in ‘Orin’ Apples (Malus domestica) at Different Ripening Stages

‘Orin’ is a popular apple cultivar, which has a yellow-green appearance, pleasant taste, and unique aroma. However, few studies on the fruit quality characteristics of ‘Orin’ apples have been reported before. In this study, changes of the physiological characteristics were measured at different ripening stages, and the soluble sugars and organic acids were determined by high-performance liquid chromatography (HPLC). Volatile compounds were identified using the headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS). During the fruit ripening, the ‘Orin’ apple fruit weight, size, and total soluble solid were gradually increased by contrast with the titratable acidity, and the firmness decreased. The content of four soluble sugars reached the maximum at the 180 days after full bloom (DAFB) stage. Malic acid was measured as the most abundant organic acid in ‘Orin’ apples. Ethyl butyrate, hexyl propanoate, hexyl acetate and butyl acetate belonging to esters with high odor activity values (OAVs) could be responsible for the typical aroma of ‘Orin’ apples. The aim of this work was to provide information on the flavor characteristics of ‘Orin’ apples and promote this apple cultivar for marketing and processing in the future.     

Bioactive Phenolic Compounds from Primula veris L.: Influence of the Extraction Conditions and Purification

Our experiments may help to answer the question of whether cowslip (Primula veris L.) is a rich source of bioactive substances that can be obtained by efficient extraction with potential use as a food additive. A hypothesis assumed that the type of solvent used for plant extraction and the individual morphological parts of Primula veris L. used for the preparation of herbal extracts will have key impacts on the efficiency of the extraction of bioactive compounds, and thus, the health-promoting quality of plant concentrates produced. Most analysis of such polyphenolic compound contents in extracts from Primula veris L. has been performed by using chromatography methods such as ultra-performance reverse-phase liquid chromatography (UPLC−PDA−MS/MS). Experiments demonstrated that the most effective extraction agent for fresh study material was water at 100 °C, whereas for dried material it was 70% ethanol. The richest sources of polyphenolic compounds were found in cowslip primrose flowers and leaves. The aqueous and ethanol extracts from Primula veris L. were characterized by a quantitatively rich profile of polyphenolic substances, and a high antioxidative potential. Selective extraction with the use of mild conditions and neutral solvents is the first step to obtaining preparations from cowslip primrose with a high content of bioactive substances.