毛细管电泳技术在药物分析中的应用研究进展

如果以毛细管区带电泳的出现为起点,毛细管电泳（capillary electrophoresis,CE）技术的起源可以追溯到20世纪60年代中期,瑞典科学家Hjerten首先提出毛细管区带电泳的概念.此后,毛细管电泳技术得到飞速发展,在常规药物分析和其他药物研究中发挥着独特的作用,如以治疗为目的的某一类药物的代谢物组学、药代动力学研究、药品质量控制、生物制品、毒物及滥用药物的定性定量分析等.CE具有高效、快速、微量、多模式、经济、自动化及洁净等优点.随着与之相关的一系列分析方法和检测联用技术的不断改进,CE在化学、生命科学、临床医学、药学等领域得到了广泛的应用.本文就近年来该技术在国内外的进展进行综述.     

大环抗生素作毛细管电泳手性选择剂的研究进展

大环抗生素是近年来运用并发展起来的一类非常有效的新型手性选择剂,对各种不同的外消旋体表现出极佳的手性分离能力。本文以不同类型的抗生素分别综述了国内外大环抗生素作为毛细管电泳手性选择剂的应用、影响手性分离的因素、大环抗生素结构特征和可能的手性识别机理,以期为正确预测电泳条件、可分离物质的类型、对映体分离的数量级及洗脱顺序等提供有价值的信息,并为寻找或设计新的具有高分离能力的手性选择试剂提供一定的理论指导。     

Recent advances in affinity capillary electrophoresis (2007)

Papers detailing the use of affinity capillary electrophoresis (ACE) in examining binding parameters between biological species are summarized in this review. The works cited in this review were published during 2007 and were drawn from the major chemical and biochemical journals and especially the major analytical chemistry literature.     

手性技术在抗生素等医药工业中的应用

对映异构体药物由于空间立体构型不同而在体内往往呈现很大的药理学等方面的差异。采用手性技术开发生产手性药物已成为世界制药工业的发展潮流。本文从拆分分离技术、手性库技术和不对称合成三个方面介绍了手性技术在抗生素等药物生产中的应用。     

毛细管电泳手性拆分机理研究进展

目的阐述近年来毛细管电泳手性拆分的机理研究进展。方法归纳国内外最新的文献报道,对目前主流的三类毛细管电泳手性识别机理研究方法进行综述。结果采用计算机分子模拟,结合毛细管电泳分析法和光谱分析法,可以从分子水平上研究毛细管电泳拆分体系的手性识别机理。结论计算机分子模拟技术已成为毛细管电泳手性拆分机理研究领域中的一种十分有力的工具。     

Recent advances in the pharmaceutical management of pain

Pain is an unpleasant sensory and emotional experience for patients. Management of pain is the most frequent issue encountered by clinicians and treatment is usually with pharmacological therapy. This review discusses recent pharmaceutical advances in pain management with respect to new modes of analgesic delivery, as well as new analgesic agents and adjuvants that are currently being investigated for their analgesic properties. New modes of administration include transdermal delivery in the form of skin patches, transmucosal delivery, inhalational administration, various patient-controlled devices and extended-release analgesic formulations. Up-to-date research is presented on classical analgesics, such as opioids, anti-inflammatory agents, including cyclo-oxygenase-2 inhibitors and paracetamol (acetaminophen), local anesthetics and ketamine. In addition, newer agents such as antidepressants and antiepileptic drugs as well as medicinal cannabinoids are discussed. As our understanding of the multiple pain pathways involved in the pathogenesis of pain expands, further compounds with analgesic properties will be developed.     

Recent advances in the pharmaceutical management of pain

Pain is an unpleasant sensory and emotional experience for patients. Management of pain is the most frequent issue encountered by clinicians and treatment is usually with pharmacological therapy. This review discusses recent pharmaceutical advances in pain management with respect to new modes of analgesic delivery, as well as new analgesic agents and adjuvants that are currently being investigated for their analgesic properties. New modes of administration include transdermal delivery in the form of skin patches, transmucosal delivery, inhalational administration, various patient-controlled devices and extended-release analgesic formulations. Up-to-date research is presented on classical analgesics, such as opioids, anti-inflammatory agents, including cyclo-oxygenase-2 inhibitors and paracetamol (acetaminophen), local anesthetics and ketamine. In addition, newer agents such as antidepressants and antiepileptic drugs as well as medicinal cannabinoids are discussed. As our understanding of the multiple pain pathways involved in the pathogenesis of pain expands, further compounds with analgesic properties will be developed.     

毛细管电泳手性拆分方法的研发策略

本文总结了毛细管电泳手性拆分的基本策略、分离条件选择策略、环糊精体系的选择,并提出毛细管电泳手性拆分方法的一般研究与开发策略,可为以后的毛细管电泳手性分离分析提供借鉴与思路。     

Strategies for rapid chiral analysis by capillary electrophoresis

The aim of this study was to investigate four strategies to decrease chiral CE analysis time: (1) short-end injection technique, (2) high electric field through a capillary length reduction, (3) external pressure application and (4) capillary dynamically coated to generate an important electroosmotic flow. These approaches were applied for a simultaneous enantiomeric separation of amphetamine and four related compounds using a neutral derivatised cyclodextrin (hydroxypropyl-beta-cyclodextrin) as chiral selector. Analysis time and CE performances, in terms of peak efficiency and resolution, were examined. Among the investigated strategies, the dynamic coating procedure appeared to be the most suitable approach to decrease analysis time (inferior to 7 min) and improve sensitivity. Furthermore, it exhibited very good migration time repeatability (0.1%). This benefit is of utmost interest in chiral analysis for an unambiguous peak identification, especially for a complex mixture such as reported in this study.     

Recent advances with liposomes as pharmaceutical carriers

Liposomes - microscopic phospholipid bubbles with a bilayered membrane structure - have received a lot of attention during the past 30 years as pharmaceutical carriers of great potential. More recently, many new developments have been seen in the area of liposomal drugs - from clinically approved products to new experimental applications, with gene delivery and cancer therapy still being the principal areas of interest. For further successful development of this field, promising trends must be identified and exploited, albeit with a clear understanding of the limitations of these approaches.     

Determination of Ziprasidone in pharmaceutical formulations by capillary zone electrophoresis

The atypical antipsychotic drug Ziprasidone was determined by capillary zone electrophoresis in pharmaceutical formulations. Extraction of the drug from the formulation consisted in a simple dissolution step with methanol as solvent, and enables determination of the drug without any interference from the excipients. It was found that at pH of the background electrolyte above 5 the peak of the drug exhibited a tailing, at pH 6 or higher even a disappearance of the peak in the electropherogram was observed. This behaviour was related to the concomitant reduction of the solubility of the drug in the background electrolyte upon deprotonation at higher pH. As a consequence, analyses were carried out with formate buffer, pH 3.0, and enabled run times of about 3 min. The method was validated in terms of stability, specificity, precision, accuracy, linearity, quantitation limits, and robustness, and was applied to the analysis of different commercial capsules.     

Recent advances in trace analysis of pharmaceutical genotoxic impurities

Genotoxic impurities (GTIs) in pharmaceuticals at trace levels are of increasing concerns to both pharmaceutical industries and regulatory agencies due to their potentials for human carcinogenesis. Determination of these impurities at ppm levels requires highly sensitive analytical methodologies, which poses tremendous challenges on analytical communities in pharmaceutical R&D. Practical guidance with respect to the analytical determination of diverse classes of GTIs is currently lacking in the literature. This article provides an industrial perspective with regard to the analysis of various structural classes of GTIs that are commonly encountered during chemical development. The recent literatures will be reviewed, and several practical approaches for enhancing analyte detectability developed in recent years will be highlighted. As such, this article is organized into the following main sections: (1) trace analysis toolbox including sample introduction, separation, and detection techniques, as well as several ‘general’ approaches for enhancing detectability; (2) method development: chemical structure and property-based approaches; (3) method validation considerations; and (4) testing and control strategies in process chemistry. The general approaches for enhancing detection sensitivity to be discussed include chemical derivatization, ‘matrix deactivation’, and ‘coordination ion spray-mass spectrometry’. Leveraging the use of these general approaches in method development greatly facilitates the analysis of poorly detectable or unstable/reactive GTIs. It is the authors’ intent to provide a contemporary perspective on method development and validation that can guide analytical scientists in the pharmaceutical industries.     

Eliminating pharmaceutical impurities: Recent advances in detection techniques

The elimination of organic impurities to produce highly pure drug substances is an important goal of process chemistry. For the detection of general impurities, hyphenated techniques (eg, liquid chromatography-mass spectrometry [LC-MS]) play a critical role in rapid structural identification (qualitative detection) and in understanding the mechanisms of formation of the impurities, enabling informed decisions to control and eliminate the impurities resulting from the chemical process where possible. Concern regarding genotoxic impurities (GTIs), which must typically be controlled at low parts-per-million limits, continues to increase, and significant advances have been achieved in recent years for the selective and sensitive quantitation (quantitative detection) of such impurities. Conventional detection techniques, such as ultraviolet (UV) detection, are often inadequate for the detection of potentially minute quantities of GTIs; therefore, various advanced MS-based detection strategies, either stand-alone or in conjunction with chemical approaches, are playing an increasing role in this field. The primary aim of this review is to highlight recent advances in qualitative and quantitative detection of impurities at trace levels, with a particular focus on GTIs.     

A strategic approach to the development of capillary electrophoresis chiral methods for pharmaceutical basic compounds using sulfated cyclodextrins.

Enantioseparations of basic pharmaceutical compounds were investigated using different types of sulfated cyclodextrins as chiral selectors. A general strategy for method development was described, together with enantiomeric separations of a number of pharmaceutical related compounds. Based on this strategy, systematic method development approaches for several selected compounds were performed by modifying method parameters, such as the concentration of the chiral selectors, buffer pH, type of organic modifiers, buffer type, temperature and applied voltage. The results of the investigation elucidated the separation mechanism. Many practical aspects were also discussed through several specific examples in order to demonstrate how to develop and validate a precise, sensitive, accurate and rugged separation.     

非水毛细管电泳在手性药物拆分中的应用

本文综述了非水毛细管电泳的分离机理、溶剂的选择、手性选择剂的种类及拆分的影响因素，并进行了其在手性药物拆分中的应用研究，列举了手性药物拆分的实例。     

Rapid determination of diclofenac in pharmaceutical formulations by capillary zone electrophoresis

Capillary electrophoresis is competitive to HPLC and other chromatographic methods, predominantly when charged analytes have to be separated. The time of analysis can be reduced by the use of very short capillaries applying a high voltage. In most instruments which are commercially available the so-called 'short end' of the capillary can be used for separation, leading to very rapid separations. In this contribution we want to demonstrate this approach by using Diclofenac Sodium as an analyte.     

Quantitative determination of alginic acid in pharmaceutical formulations using capillary electrophoresis

A capillary electrophoresis (CE) method has been developed and validated for the quantitative determination of alginic acid, which is used as a rafting agent in complex antacid formulations. The method involves a preliminary separation of the alginic acid from the formulation by washing the sample matrix with methanol, diluted HCl and water. This is followed by electrophoresis within a fused silica capillary using borate/boric acid buffer as the electrolyte, and the quantification is performed by a UV detector monitoring at 200 nm, where the intrinsic absorption of alginic acid is measured. An assay precision of better than 3% was achieved in intra- and interday determinations. No interference was found from the matrix of the antacid formulations.     

SELEX技术及寡核苷酸适配体的近期研究进展

指数富集的配体系统进化（SELEX）技术是一类具备蓬勃发展前景的体外筛选技术,在生物学、药学及化学领域已引起广泛关注。本文即针对2004年以来SELEX技术的发展特点,主要介绍两类新型SELEX策略,即毛细管电泳-SELEX和针对复杂靶标的SELEX方法,并简要总结了寡核苷酸适配体在生物医学和药学相关方面的最新应用进展。     

Recent advances in the therapeutic applications of pyrazolines

INTRODUCTION: Pyrazolines are well-known and important nitrogen-containing five-membered ring heterocyclic compounds. Various methods have been worked out for their synthesis. Several pyrazoline derivatives have been found to possess diverse biological properties, which has stimulated research activity in this field. AREAS COVERED: The present review sheds light on the recent therapeutic patent literature (2000 - 2011) describing the applications of pyrazolines and their derivatives on selected activities. Many of the therapeutic applications of pyrazoline derivatives have been discussed, either in the patent or in the general literature areas in this review. In addition to selected biological data, a wide range of pharmaceutical applications and pharmaceutical compositions are also summarized. EXPERT OPINION: Pyrazoline derivatives have numerous prominent pharmacological effects, such as antimicrobial (antibacterial, antifungal, antiamoebic, antimycobacterial), anti-inflammatory, analgesic, antidepressant and anticancer. Further pharmacological effects include cannabinoid CB1 receptor antagonists, antiepileptic, antitrypanosomal, antiviral activity, MAO-inhibitory, antinociceptive activity, insecticidal, hypotensive, nitric oxide synthase inhibitor, antioxidant, steroidal and antidiabetic. Lastly, they also effect ACAT inhibition, urotensin II and somatostatin-5 receptors, TGF-β signal transduction inhibitors and neurocytotoxicity inhibitors activities. Many new pyrazoline derivatives have been synthesized and patented, but there are still new aspects to explore and work on.