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生物药学系

顾景凯

日期:2020-08-11 点击数: 来源:

顾景凯

姓名: 顾景凯
职位: 教授
最高学位: 博士
电话: 0431-85155380
Email: gujk@jlu.edu.cn
工作地点: 吉林省长春市前进大街2699号生命科学楼

研究方向:

药物代谢动力学;体内药物分析;生物质谱分析;靶点药物分析;纳米药物体内多形态成分分析;多糖、ADC及蛋白肽类等生物大分子药物分析;高分子药用辅料质量控制与体内评价;新型给药系统的体内时空命运研究;基于DMPK的新药设计与开发。

教育经历:

1997年至2000年 新葡的京集团8814超分子结构与材料国家重点实验室,博士后。

1994年至1997年 沈阳药科大学药学院,药物分析,博士;

工作经历:

现任新葡的京集团8814唐敖庆特聘教授;兼任新葡的京集团8814艾滋病疫苗国家工程实验室、分子酶学工程教育部重点实验室,教授。

2012-01-至今,新葡的京集团8814,唐敖庆特聘教授

2003-12-至今,新葡的京集团8814,新葡的京集团8814药物代谢研究中心主任,教授,博士生导师

2001-09,新葡的京集团8814,破格晋升为“激励岗”教授

2000-01至2001-09,新葡的京集团8814,新葡的京集团8814,副教授

学术兼职:

兼任国家药品监督管理局药品注册审评专家咨询委员会专家;中国医药质量管理协会临床研究质量与评价专业委员会,副主任委员;国家药品监督管理局“药用辅料质量研究与评价重点实验室”学术委员会,委员;国家中医药管理局“中药药代动力学三级实验室”,主任;中国生化制药协会专家委员会,委员;全国工商联医药业商会专家;中国药理学会:药物代谢专业委员会、临床药理专业委员会、药物基因组专业委员会、分析药理专业委员会,常务委员;中国药学会:药物分析专业委员会、应用药理学会专业委员会,常务委员;中国医药生物技术协会药物分析技术分会,常务委员;吉林省药理学会副理事长;中国质谱学会有机质谱专业委员会,委员;美国化学会(ACS),会员;国际药物及化学异物代谢学会(ISSX),会员。

荣誉称号:

新葡的京集团8814“唐敖庆”特聘教授

新葡的京集团8814“十一五”科技突出贡献奖。

军队特需新药临床研究关键技术平台构建与应用,中国人民解放军总后勤部,省部级二等奖,2011

研究成果:

主持科研项目

1.国家自然科学基金委员会,重点项目,No.82030107, 药物载体递送系统体内时空命运研究,2021-01至2025-12, 297万元,在研,主持;

2.国家自然科学基金委员会,重点项目,No.81430087, 桥接细胞与整体的纳米药代动力学研究,2015-01至2019-12, 320万元,已结题,主持;

3. 国家卫生健康委员会,“十一五”重大新药创制专项,2009ZX09304-003,临床前药物代谢动力学技术平台(子课题),2009-01至2010-12, 326.16万元,已结题,主持;

4. 国家卫生健康委员会,“十三五”重大新药创制专项,2017ZX09101001,药物一致性评价关键技术与标准研究子课题“离子淌度串联质谱突破体内药物分析强干扰瓶颈:极低剂量药物BE一致性评价新技术”, 2017-01至2020-12, 260万元,已结题,主持;

5. 江苏省科技成果转化专项资金,BA2010147,治疗老年性痴呆的1.1类化学新药-琥珀八氢氨吖啶片的临床研究及产业化,2010至2016,600万元,已验收,主持;

6. 国家自然科学基金委员会,面上项目,No.81872831,基于质谱新技术的PEG-PLA紫杉醇纳米胶束体内多形态成分的精准分析,2019-01至2022-12,57万元,在研,主持;

7. 国家自然科学基金委员会,面上项目,No.81673396,基于SWATH技术的PEG化药物LC-HR-MS/MS分析方法研究与应用,2017-01至2020-12,70万元,已结题,主持;

8. 国家自然科学基金委员会,面上项目,No.30973587,微管靶向型药物的亚细胞水平药代动力学研究,2010-01至2012-12,25万元,已结题,主持;

9. 国家自然科学基金委员会,面上项目,No.30772613,七叶皂苷四组分同时给药的代谢机理及相互关系研究,2008-01至2010-12,30万元,已结题,主持;

10. 国家自然科学基金委员会,面上项目,No.30070879,关于药物的葡萄糖醛酸化代谢研究,2001-01至2003-12,15万元,已结题,主持;

11. 科技部,“十二五”国家科技支撑计划,2012BAI30B02,维吾尔、哈萨克药生物活性成分筛选和现代标准组分库建设(子课题),2012.01至2014.12,30万元,已结题,主持;

12. 国家卫计委,“十一五”重大新药创制专项,2008ZX09101-020,注射用洋参叶总皂苷的临床研究(子课题),2010-11至2011-10,11万元,已结题,主持;

13. 科技部国际合作项目,S2010GR0920,通过联合给药技术提高青蒿素类药物的生物利用度、降低疟疾耐药性(子课题),2009-9至2011-12,35万元,已结题,主持;

14. 科技部,“十一五”国家科技支撑计划,2006BAI11B07,中医药诊疗技术及特色产品应用研究:中医药治疗糖尿病的代谢组学研究(子课题),2009至2011,28万元,已结题,主持;

15. 科技部,“十一五”重大新药创制专项,军用特需药课题,2009zxj09014-0097,“动物模型关键技术”新药防耐药突变浓度检测与组织内药物浓度测定(子课题),2009-1至2010-12,30万元,已结题,主持;

16. 国家中医药管理局,2006BAI09B09-08,中药缓控释制剂多组分释放评价技术及其适宜性应用(子课题),2006-10至2009-10,8万元,已结题,主持;

17. 吉林省科技厅,20040412-1,治疗老年痴呆的一类新药神尔洋的研究,2006-01至2007-12,20万元,已结题,主持。

横向课题:

(一)生物等效性课题

利马前列腺素、前列地尔、阿霉素脂质体、两性霉素B脂质体、PEG-PLA紫杉醇胶束、盐酸二甲双胍、佐米曲普坦、左羟丙哌嗪、盐酸非索非那定、舍曲林、奥美拉唑、替米沙坦、吲哒帕胺、亮菌甲素、米格列醇、阿奇霉素、氨溴索、氨氯地平、格列吡嗪、曲尼司特、多潘立酮、磷霉素钙、依那普利、氟桂利嗪、阿那曲唑、格列美脲、纳美芬、阿莫西林克拉维酸钾、阿伦磷酸钠、阿夫唑嗪、雷尼替丁、西沙必利、格列美脲、罗红霉素、石杉碱甲、愈酚甲麻那敏、氢氯噻嗪、特拉唑嗪、辛伐他汀、左炔诺孕酮、塞洛多辛、瑞格列奈、洛伐他汀、氯雷他定、盐酸特比萘芬、瑞舒伐他汀钙、阿戈美拉汀、氯沙坦钾、结合型雌激素、胡黄连总苷、雷贝拉唑、群多普利、甲磺酸地拉韦啶、盐酸沙格雷酯。

(二)临床药代动力学课题

埃他卡林、卡托普利、精氨酸七叶皂苷、重组人胸腺素α1、洛伐他汀、克拉霉素、阿奇霉素、氨咖敏甲麻胶囊、复方缬沙坦分散片、复方酚咖伪麻胶囊、甘草酸二胺、右美沙芬、依卡倍特、匹伐他汀、非洛地平、米屈肼、美托洛尔、普卢利沙星、非索非那定、伪麻黄碱、羟考酮、倍氯米松、硝酸甘油软膏、氨基葡萄糖、帕拉米韦三水合物、甲萘氢醌二磷酸酯钠、烟酸、沙利度胺、奥普力农、雷贝拉唑、氯沙坦钾、依非巴特、兰地洛尔、注射用头孢替坦二钠、注射用左旋泮托拉唑钠、苯磺酸氨氯地平叶酸、盐酸头孢卡品酯、盐酸氨溴索、盐酸阿那格雷、伊潘立酮、利马前列腺素、石杉碱甲、来那度胺、异丙肌苷、氯法拉滨、磷酸瑞格列汀、脯氨酸恒格列、双环醇等。

(三)临床前药代动力学课题

PEG-PLA、葡聚糖、原人参二醇、氨苄西林/丙磺舒、水杨酸伪麻黄碱、华洋-001、TJW-01、FY-01、WZA-001、石杉碱甲微球、葫芦素、WZA-001、JSTHSYY、赖氨酸七叶皂苷钠、头孢呋辛/丙磺舒、奥曲肽微球、利拉鲁肽、索马鲁肽、曲普瑞林、亮丙瑞林、WZA-001、39肽、益今生、苯胺洛芬、赖氨酸七叶皂苷、伪人参皂苷GQ、秋水仙碱控释片、利培酮微球、前列地尔胶束、奥曲肽微球、替莫唑胺颅内缓释植入片、替莫唑胺酯栓、利培酮微球(30L)、次血红素六肽、LY03005、落新妇苷、帕潘立酮、左旋泮托拉唑钠、重组人胸腺素α1、胸腺五肽-胸腺七肽、苯胺洛芬滴眼液、卡前列甲酯片、达瑞司他、小檗碱、复达那非、BT100X、右旋兰索拉唑、艾塞那肽、猪松弛素、青霉素钠/丙磺舒钠。

近五年代表性期刊论文:

1.Bai, Ruifeng,Sun ,Dong,Shan, Yuqin, Guo, Zhiqiong, Chu, Dafeng , Fawcett, John Paul, Gu, Jingkai*,Disposition and fate of polyoxyethylene glycerol ricinoleate as determined by LC-Q-TOF MS coupled with MSALL, SWATH and HR MS/MS techniques. CHINESE CHEMICAL LETTERS (32) 3237-3240,2021,10

2.Meng, Xiangjun, Zhang, Zhi,Tong, Jin, Sun, Hui, Fawcett, John Paul, Gu, Jingkai* The biological fate of the polymer nanocarrier material monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid) in rat. ACTA PHARMACEUTICA SINICA B (11):1003-1009,2021 .4

3. Zhang Z, Jiang H, Zhang Y, Zhang D, Fawcett JP, Gu J*. Comprehensive Bioanalysis of Ultrahigh Molecular Weight, Highly Disperse Poly(ethylene oxide) in Rat via Microsolid Phase Extraction and RPLC-Q-Q-TOF Coupled with the MSALL Technique. Anal Chem. 2020; doi: 10.1021/acs.analchem.0c00189.

4. Zhang Z, Zhang Y, Song S, Yin L, Sun D, Gu J*. Recent advances in the bioanalytical methods of polyethylene glycols and PEGylated pharmaceuticals. J Sep Sci. 2020; doi: 10.1002/jssc.201901340.

5. Wang T, Guo Y, He Y, Ren T, Yin L, Fawcett JP, Gu J*, Sun H*. Impact of molecular weight on the mechanism of cellular uptake of polyethylene glycols (PEGs) with particular reference to P-glycoprotein. Acta Pharm Sin B. 2020; doi:10.1016/j.apsb.2020.02.001

6. Wang H, Zheng M, Gao J, Wang J, Zhang Q, Fawcett JP, He Y*, Gu J*. Uptake and release profiles of PEGylated liposomal doxorubicin nanoparticles: A comprehensive picture based on separate determination of encapsulated and total drug concentrations in tissues of tumor-bearing mice. Talanta.2020; 208:120358.

7. Yin L, Ren T, Zhao S, Shi M*, Gu J*. Comparative pharmacokinetic study of PEGylated gemcitabine and gemcitabine in rats by LC-MS/MS coupled with pre-column derivatization and MSALL technique. Talanta. 2020; 206: 120184.

8. Su C, Liu Y, Li R, Wu W, Fawcett JP, Gu J*. Absorption, distribution, metabolism and excretion of the biomaterials used in Nanocarrier drug delivery systems. Adv Drug Deliv Rev. 2019; 143: 97-114.

9. Yin L, Zhang Z, Liu Y, Gao Y, Gu J*. Recent advances in single-cell analysis by MSspectrometry. Analyst. 2019;144:824-845.

10. Yin L, Feng Y, Tong J, Guo Z, Zhang Y, Zhang Q, Sun Y, Fawcett JP, Gu J*. Ultrahigh-throughput absolute quantitative analysis of linezolid in human plasma by direct analysis in real time mass spectrometry without chromatographic separation and its application to a pharmacokinetic study. Anal Bioanal Chem. 2019;411:5139-5148.

11. Wang T, Yin L, Wang H, Fawcett JP, Gu J*. Development and application of a high-throughput liquid chromatography-tandem mass spectrometric method for the simultaneous determination of thymosin α1 and its recombinant human form in plasma and urine. J Pharm Biomed Anal. 2019;170:16-21.

12. Ren T, Zhang Z, Fawcett JP, Sun D*, Gu J*. Micro-solid phase extraction and LC-MS3 for the determination of triptorelin in rat plasma and application to a pharmacokinetic study. J Pharm Biomed Anal. 2019;166:13-19.

13. Zhang Z, Li R, Liu S, Yin L, Xu T, Fawcett JP, Gu J*. Liquid chromatography tandem mass spectrometry with triple stage fragmentation for highly selective analysis and pharmacokinetics of alarelin in rat plasma. J Sep Sci. 2019;42:3033-3040.

14. Liang C, Sun H, Meng X, Yin L, Fawcett JP, Yu H, Liu T, Gu J*. Separation and simultaneous quantitation of PGF2α and its epimer 8-iso-PGF2α using modifier-assisted differential mobility spectrometry tandem mass spectrometry. Acta Pharm Sin B. 2018;8:228-234.

15. Lin W, Yin L, Sun T, Wang T, Xie Z, Gu J*, Jing X*. The Effect of Molecular Structure on Cytotoxicity and Antitumor Activity of PEGylated Nanomedicines. Biomacromolecules. 2018;19:1625-1634.

16. Su C, Liu Y, He Y*, Gu J*. Analytical methods for investigating in vivo fate of nanoliposomes: A review. J Pharm Anal. 2018;8:219-225.

17. Sun D, Su C, Liu Y, Meng X, Fawcett JP, Guo Y, Gu J*. A Unique Collision-Induced Dissociation Reaction of Cholamine Derivatives of Certain Prostaglandins. J Am Soc Mass Spectrom. 2018;29:2360-2367.

18. Sun D, Meng X, Ren T, Fawcett JP, Wang H, Gu J*. Establishment of a Charge Reversal Derivatization Strategy to Improve the Ionization Efficiency of Limaprost and Investigation of the Fragmentation Patterns of Limaprost Derivatives Via Exclusive Neutral Loss and Survival Yield Method. J Am Soc Mass Spectrom. 2018; 29:1365 -1375.

19. Su C, Yang H, Sun H, Fawcett JP, Sun D*, Gu J*. Bioanalysis of free and liposomal Amphotericin B in rat plasma using solid phase extraction and protein precipitation followed by LC-MS/MS. J Pharm Biomed Anal. 2018;158:288-293.

20. Ren T, Li R, Meng X, Fawcett JP, Sun D*, Gu J*. Differential mobility spectrometry followed by tandem mass spectrometry with multiple ion monitoring for bioanalysis of eptifibatide in rat plasma. J Pharm Biomed Anal. 2018 ;151:260-265.

21. Zhou X, Meng X, Cheng L, Su C, Sun Y, Sun L, Tang Z, Fawcett JP, Yang Y*, Gu J*. Development and Application of an MSALL-Based Approach for the Quantitative Analysis of Linear Polyethylene Glycols in Rat Plasma by Liquid Chromatography Triple-Quadrupole/Time-of-Flight Mass Spectrometry. Anal Chem. 2017;89:5193-5200.

22. Cong Y, Hu L*, Zhang Z, Gao Y, Dong M, Qin H, Ye M*, Gu J, Zou H. Analysis of therapeutic monoclonal antibody glycoforms by mass spectrometry for pharmacokinetics study.Talanta,2017, 165:664-670.

23. Yin L, Su C, Ren T, Meng X, Shi M, Paul Fawcett J, Zhang M, Hu W, Gu J*. MSALL strategy for comprehensive quantitative analysis of PEGylated-doxorubicin, PEG and doxorubicin by LC-high resolution q-q-TOF mass spectrometry coupled with all window acquisition of all fragment ion spectra. Analyst. 2017 ;142:4279-4288.

24. Su C, Sun H, Yang H, Yin L, Zhang J, Fawcett JP, Gu J*. A validated UPLC-MS/MS method coupled with protein precipitation and ion exchange solid phase extraction for the quantitation of porcine relaxin B29 in dog plasma and its application to a pharmacokinetic study. Anal Bioanal Chem. 2017;409:6559-6565.

25. Meng X, Xu H, Zhang Z, Fawcett JP, Li J, Yang Y*, Gu J*. Differential mobility spectrometry tandem mass spectrometry with multiple ion monitoring for the bioanalysis of liraglutide. Anal Bioanal Chem. 2017;409:4885-4891.

26. Sun H, Zhang Q, Zhang Z, Tong J, Chu D*, Gu J*. Simultaneous quantitative analysis of polyethylene glycol (PEG), PEGylated paclitaxel and paclitaxel in rats by MS/MSALL technique with hybrid quadrupole time-of-flight mass spectrometry. J Pharm Biomed Anal. 2017;145:255-261.

27. Su C, Yang H, Meng X, Fawcett JP, Cao J, Yang Y*, Gu J*. Determination of rabeprazole enantiomers in dog plasma by supercritical fluid chromatography tandem mass spectrometry and its application to a pharmacokinetic study. J Sep Sci, 2017, 40:1010- 1016.

28. Lu H, Su C, Yin L, Gu L, Gu J*, Chen X*. Liquid chromatography-tandem mass spectrometry method for simultaneous determination of valproic acid and its ene-metabolites in epilepsy patient plasma. J Pharm Anal. 2016; 6: 112-116.

29. Yang Z, Xu X, Sun L, Zhao X, Wang H, Fawcett JP, Yang Y*, Gu J*. Development and validation of an enantioselective SFC-MS/MS method for simultaneous separation and quantification of oxcarbazepine and its chiral metabolites in beagle dog plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2016, 1020: 36-42.

29. Sun H, Wang J, Sun Y, Peng W, Sun L, Yang Y*, Gu J*. Rapid and sensitive liquid chromatography with tandem mass spectrometry method for the simultaneous quantification of yonkenafil and its major metabolites in rat plasma. J Sep Sci. 2016, 39:3700-3708.

30. Yang Z, Sun L, Liang C, Xu Y, Cao J, Yang Y*, Gu J. Simultaneous quantitation of the diastereoisomers of scholarisine and 19-epischolarisine, vallesamine, and picrinine in rat plasma by supercritical fluid chromatography with tandem mass spectrometry and its application to a pharmacokinetic study. J Sep Sci. 2016, 39:2652-60.

31. Yang Z, Wang L, Xu M, Gu J, Yu L, Zeng S*. Simultaneous analysis of gemfibrozil, morphine, and its two active metabolites in different mouse brain structures using solid-phase extraction with ultra-high performance liquid chromatography and tandem mass spectrometry with a deuterated internal standard. J Sep Sci. 2016; 39:2087-96.

32. Yin L, Wang T, Shi M, Zhang Y, Zhao X, Yang Y*, Gu J*. Simultaneous determination of ten antiepileptic drugs in human plasma by liquid chromatography and tandem mass spectrometry with positive/negative ion-switching electrospray ionization and its application in therapeutic drug monitoring. J Sep Sci. 2016,39:964-72.

专利:

1. 顾景凯;尹磊;任天明;赵式樱;史美云;林文孩;景遐斌。一种PEG及PEG化药物的分析检测方法及其应用:中国, CN201710706546.2. 2018-01-16.

2. 顾景凯;孟祥骏;赵式樱;张琪;僮金;尹磊。一种定量测定生物样品中前列腺素的方法:中国, CN201710707523.3. 2018-01-19.

3. 顾景凯;徐学宇;王浩;赵雪。一种噻吩并吡啶类衍生物硫酸氢盐的晶型Ⅲ及其制备方法和应用:中国,CN201710700259.0. 2017-11-24.

4. 顾景凯;徐学宇;王浩;赵雪。一种噻吩并吡啶类衍生物硫酸氢盐的晶型Ⅱ及其制备方法和应用:中国,CN201710700262.2. 2019-08-16.

5. 顾景凯;张扬;杨志超;尹磊。一种脑靶向艾司利卡西平酯类前药及其应用:中国,CN201611039363.1. 2019-09-27.

6. 顾景凯;周晓彤;程龙妹;尹磊;杨艳。一种生物样本中PEG含量的测定方法:中国,CN201510356323.9. 2017-03-29.

7. 顾景凯;尹磊;史美云;孟祥骏;宿崇;彭雯雯;陆欢;林文孩;杨艳;景遐斌。一种生物样本中PEG化药物的定量测定方法:中国,CN201510356568.1. 2017-04-05.

8. 顾景凯;张扬;杨艳;赵森;杨智超;杨弘;宿崇。脑靶向O-去甲基文拉法辛酚酯类前药及制备方法和用途:中国, CN201310527939.9. 2015-07-22.

出版专著:

《缓控释制剂药物动力学》,科学出版社,2009年,合作主编

《临床药物动力学》,科学出版社,2010年,编委

学术会议:

1. Studies on the Fate of Nano-drug Delivery System in vivo, 4TH Ling-Nan International Forum on DMPK,广州,2019.

2. LC-MS for Bioanalysis of Therapeutic Peptides, Polymer Excipient and Nano-DDS, CPSA(Pharnaceutical Solutions through Analysis), 上海,2019.

3. Studies on DMPK of Nano-Carriers in vivo, The 2nd International Symposium on Advances in Pharmaceutical Analysis,法国里尔市,2018.

4. ASMS Conference on Mass Spectrometry and Allied Topics,美国加利福尼亚洲,圣地亚哥市,2018.

5. ASMS Conference on Mass Spectrometry and Allied Topics,美国印第安纳州,印第安纳波利斯市,2017.

6. DMPK of Nano-DDS: Challenge and Our Strategies, Asian Federation of Pharmaceutical Sciences Conference 2017,厦门,2017.

7. Development of LC-HR-MS/MS with the swath technique for pharmacokinetic studies of PEG and pegylated drugs, 27th International Symposium on Pharmaceutical and Biomedical Analysis (PBA 2016),广州,2016.