In depth Seminar on drug separation, purification, structure identification and assignment

Background: in the process of drug development and production, impurity control is a key issue related to drug quality Regulations such as ichq3a, ichq3b and nmpa technical guidelines for impurity research of chemical drugs also put forward clear requirements for impurity research In the research process of organic impurities, including process impurities and degradation impurities, how to obtain impurities, how to identify the structure of unknown impurities, and how to calibrate and assign impurities so that they can be used as standards, have always been the hot and difficult points for pharmaceutical researchers In the analysis of drug impurities, the traditional RP-HPLC method often uses non-volatile phosphate and other buffers as the water phase, which can not be directly identified by high-resolution mass spectrometry Through the use of two-dimensional liquid chromatography system, without changing the original mobile phase separation conditions, target impurities can be collected and enriched from one-dimensional liquid chromatography In two-dimensional liquid chromatography, volatile mobile phase can be directly used and accurate qualitative analysis can be carried out by high-resolution mass spectrometry, which has gradually become a popular impurity analysis method Preparative chromatography is a powerful tool for the extraction of organic impurities By means of forward and reverse preparative chromatography, supercritical fluid chromatography and other tools for impurity enrichment, separation and purification, impurity standards can be effectively obtained in the shortest time, and then combined with NMR, MS, EA, IR, UV and other analytical methods for structural identification and standardization It is also a challenge for drug analysts to enlarge the analytical chromatogram, track and collect impurities, ensure the stability of impurities in the separation process, speculate the unknown structure, calibrate and assign trace compounds On the other hand, through flash fast chromatography, high-efficiency preparative chromatography, supercritical fluid chromatography and other tools, impurities can be separated, purified and enriched quickly and cheaply to obtain high-purity impurity standards, and then combined with NMR, MS, EA, IR, UV and other means for structure identification and standardization It is also a challenge for drug analysis and separation personnel to enlarge the analytical chromatogram, track and collect impurities, ensure the stability of impurities in the separation process, speculate the unknown structure, calibrate and assign trace compounds With the successful development and commercialization of various types of chiral stationary phases, the preparation of chromatographic separation technology using chiral stationary phases as separation medium, such as supercritical fluid chromatography and simulated moving bed chromatography, has opened up a new way for the acquisition of single enantiomers and intermediates At the same time, it is a challenge for drug R & D and production to obtain high-purity API through large-scale preparative chromatography, especially industrial preparative chromatography meeting GMP certification requirements The "2019 deep Seminar on drug separation, purification, structure identification and assignment" sponsored and sponsored by "incendiary medicine" and "manluyao Research Society" and co organized by Mingjie medicine will be held in Nanjing from May 29 to 30, 2019 The seminar will invite well-known experts in the industry for in-depth sharing and discussion, and help pharmaceutical R & D and production enterprises to continuously improve the R & D level of separation and purification, structure identification and assignment Sponsor Mingjie pharmaceutical Planning Co organized by burn medicine manlu Pharmaceutical Research Co organized by Gu Kai and Yuan Dong'an, time: May 29-30, 2019 (registration on May 28), location: Nanjing Shuguang International Hotel Support SEMER Fisher Scientific (China) Co., Ltd., Novartis separation technology (Shanghai) Co., Ltd., spectrum analysis technology (Suzhou) Co., Ltd., Anhui flying Pharmaceutical Technology Co., Ltd., Canada ACD / labs company, Research Service Department of Wuxi Pharmaceutical Co., Ltd., KANGLONG Huacheng (Beijing) new drug Technology Co., Ltd., Sailu pharmaceutical chiral technology (Shanghai) Co., Ltd Solicitation support institutions: this conference can provide enterprises and institutions with various forms of publicity and exhibition, such as naming salon, venue booth, venue advertisement, color pages of the Conference Journal, etc "conference schedule" on May 29, 2019 am 8:30-12:00 08:30-08:45 speech by the sponsor 08:45-10:15 speech topic: strategies for impurity separation and structure identification and impact on drug research and Development Speech Abstract: Impurity research is an important aspect of drug research, which runs through the whole process of drug research The analysis, separation and structure identification of impurities play an important role not only in new drugs but also in the research and development of generic drugs Whether the impurities in drugs can be controlled reasonably and effectively is directly related to the quality controllability and safety of drugs This report will introduce the basic requirements of international and domestic drug regulatory agencies for impurity research, and discuss the ideas and main methods of impurity analysis, separation and structure identification with specific examples, as well as the important influence of impurity structure identification on Optimization of API synthesis process Speaker: Dr Su Baoning, core analysis department (vice president) of Shanghai Pharmaceutical mingkant new drug development Co., Ltd 10:15-10:30 tea break / rest 10:30-12:00 speech topic: qualitative analysis of impurities in drug research and development of impurity reference materials Abstract: 1) Qualitative methods of impurities in drug research; 2) quantitative methods of impurities in drug research; 3) necessity of using impurity reference materials; 4) standardization ideas of impurity reference materials; 5) case introduction Speaker: Dr Shan Guangzhi, head of analysis and test center, Institute of pharmaceutical biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, 12:00-14:00 lunch / lunch break, May 29, 2019 PM 14: 00-18:00 14:00-14:30 topic: separation and identification of drug impurities based on modern separation and analysis technology Abstract: LC-MS (qtof-ms and iontrap-ms) can identify drug impurities online quickly Based on my team's experience, more than 80% of drug impurities can be identified accurately only based on mass spectrometry pyrolysis analysis Although LC-MS can effectively identify drug impurities, time-consuming and laborious impurity separation and preparation can not be avoided However, if based on the structural characteristics of separation and interferences, it is flexible to select separation Method, can surprise, twice the result with half the effort! Speaker: Dr Liu Guozhu, director of analytical technology, dongyangpharmaceutical Research Institute, 14:30-15:50 speech title: application of chiral chromatography technology in drug separation and purification Abstract: in the past 20 years, chiral chromatography technology has developed rapidly High performance liquid chromatography (HPLC), supercritical fluid chromatography (SFC) and chiral simulated moving bed chromatography (SMB) are widely used in the research and production of chiral drugs They are closely complementary to asymmetric catalysis, biotransformation and crystallization, and become a powerful tool for accelerating the research and development of chiral drugs This lecture will focus on the characteristics and technical advantages of chiral chromatography, the latest development of chiral stationary phase, and the case sharing of chromatography in the analysis and preparation of chiral drugs Speaker: Dr Chen Xiaoming, general manager of dailu pharmaceutical chirality Technology (Shanghai) Co., Ltd 15:50-16:10 tea break / rest 16:10-16:40 speech title: using artificial intelligence and knowledge base to analyze unknown impurity structure speech Abstract: using knowledge base to analyze unknown impurity structure example: using artificial intelligence technology to analyze unknown impurity structure example Speaker: manager Yan Zuowei, ACD / labs, China 16:40-18:00 speech title: separation, purification and structure identification of chemical components of traditional Chinese medicine speech Abstract: the chemical components of traditional Chinese medicine are diverse in structure and complex in composition, with many homologues and isomers, so it is difficult to separate them Taking Huluba, Dai Baijie and other traditional Chinese medicines as examples, this paper introduces the general methods and strategies for the separation, purification and structure identification of the chemical components of traditional Chinese medicine, providing reference for the separation and identification of impurities in the research and development of chemical drugs Speaker: welcome dinner at 18:00-19:00, Institute of radiation medicine, Research Institute of military medicine, researcher Ma Baiping, May 30, 2019, am 8:45-12:00, 08:45-10:15, speech topic: solving the problem of purification of chiral compounds and isomers by multiple technical means Abstract: in the process of drug development and production, various impurities will inevitably be produced Purification of impurities by traditional preparative chromatography has become a conventional method, but there are some problems in traditional preparative chromatography, such as slow speed and complex post-processing Supercritical carbon dioxide is used as the main eluent in SFC, which has the advantages of high speed, good separation effect and simple post-treatment For the separation of chiral compounds and various isomers, supercritical chromatography is more overwhelming It can not only solve the problem of separation of chiral compounds by chiral column, but also solve all kinds of isomers or samples that are not suitable for reverse phase separation by non chiral SFC column Speaker: Dr Liu Lei, director of separation Office of kanglonghuacheng (Beijing) new drug Technology Co., Ltd 10:15-10:30 tea break / rest 10:30-12:00 speech topic: structural analysis strategy of trace impurities Abstract: guided by the concept of QBD, according to the specific chromatographic conditions, using a variety of desalting and deacidification technologies, to achieve the seamless docking between the conventional chromatographic conditions and LC / MSN detection, using the "diagnostic fragment ion extension strategy" to infer the chemical structure of impurities, and to explore and solve the problem of structural identification of trace impurities in antibiotics Speaker: Dr yuan yaozuo, Jiangsu Institute of food and drug supervision and inspection, 12:00-14:00 lunch / lunch break, May 30, 2019 PM 14:00-18:05 14:00-15:20 speech topic: research strategy and case analysis of unknown impurities in drugs Abstract: unknown impurities in drugs have always been a difficult problem for drug quality researchers Trace unknown impurities in drugs may come from their starting materials, reagents, process by-products, degradation impurities and other possible situations However, it is impossible to determine the degree of toxicity and harm without obtaining the clear structure of impurities, so the acquisition of trace unknown impurities will be particularly important The lecturer analyzes the classification of impurities, the separation principle of impurities, the confirmation requirements of impurity structure, the assignment of impurities, the toxicity evaluation of impurities, and the study of correction factors of impurities based on the impurity research laws and policies, and shares the experience with the actual cases Speaker: Zhu Zifeng, deputy general manager of Mingjie pharmaceutical 15:20-15:40 tea break / rest 15:40-16:40 speech title: USP / EP Monograph (Monograph) case analysis and explanation and standard / reference material calibration method speech Abstract: ✦ USP / EP cases and Monograph (Monograph) case analysis and explanation; ✦ classification, management and case analysis of working standards / reference standards; ✦ calibration of standards (including impurity standards): comparison of external standard method and area normalization method, COA of test report and retest period setting and other speakers: Senior Chemist, senior scientist of USP, former US Pharmacopoeia of Wu Siqing, executive vice president of Nanjing Red Sun Pharmaceutical Research Institute 16: 40-18:00 speech topic: Research on the separation and analysis method of drug trace impurities Abstract: the analysis and research of drug impurities is the key step of drug quality control, and also an important link in the process of new drug development The United States Pharmacopoeia and European Pharmacopoeia have clear regulations on impurities, that is to say, the structure of impurities containing more than 0.1% in the drug must be determined before clinical use However, for the analysis and research of these trace components, if we use conventional separation methods to get enough pure compounds, and then use NMR, IR, UV-Vis or X-ray for structure identification, it is very time-consuming and labor-consuming In response to this challenging task, our research team has been committed to the construction of modern analytical techniques and new methods for separation and enrichment of trace impurities in drugs in recent years, and has obtained some meaningful research progress and achievements The purpose of this report is to briefly introduce our work in trace analysis