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Enantioselective high-performance liquid chromatographic assay for determination of the enantiomers of a new anti-ulcer agent,E3810, in Beagle dog plasma and rat plasma
Institution:1. Section of Drug Metabolism and Pharmacokinetics, Tsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-26, Japan;2. Section of Physical and Analytical Chemistry, Tsukuba Research Laboratories, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-26, Japan;1. Thermofisher Scientific Corporation, Beijing 10080, China;2. Key Lab of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China;3. Thermofisher Scientific Corporation, Chelmsford 01824, USA;4. Henan Institute of Veterinary Drug Control, Zhengzhou 450008, China;1. National Key Laboratory of Science and Technology on Micro/Nano Fabrication, Shanghai Jiao Tong University, Shanghai 200240, China;2. Key Laboratory of Thin Film and Microfabrication Technology, Ministry of Education, Department of Micro/Nano Electronics, Shanghai Jiao Tong University, Shanghai 200240, China;3. Faculty of Chemistry, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdańsk, Poland;1. Department of Pharmaceutical Chemistry, Sharad Pawar College of Pharmacy, Wanadongri, Hingna Road, Nagpur, 441 110, India;2. Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Amravati Road, Nagpur, 440 033, M.S, India;3. College of Pharmacy, National University of Science and Technology, Muscat, Oman;1. Laboratório Farmacêutico da Marinha, Av. Dom Hélder Câmara, 315, 20911-291 Rio de Janeiro, Brazil;2. Mestrado Profissional em Gestão, Pesquisa e Desenvolvimento na Indústria Farmacêutica, Farmanguinhos/Fiocruz, Av. Cmte. Guaranys, 447, 22775-903 Rio de Janeiro, Brazil;3. Programa de Pós-Graduação em Química, Universidade Federal Fluminense, Outeiro São João Batista, s/n°, 24210-130 Niterói, Brazil;4. Laboratório de Micro e Nanotecnologia, Farmanguinhos/Fiocruz, Av. Brasil, 4036, 21040-361 Rio de Janeiro, Brazil;5. Programa de Pós-Graduação em Engenharia e Ciência de Materiais, Universidade Federal de São Paulo, Rua Talim 330, 12231-280 São José dos Campos, Brazil;6. Departamento de Materiais e Tecnologia, Universidade Estadual Paulista, Av. Dr. Ariberto Pereira da Cunha, 333, 12516-410 Guaratinguetá, Brazil;7. Facultad de Matemática, Astronomía, Física y Computación, Universidad Nacional de Córdoba, Medina Allende, Ciudad Universitaria, X5000HUA Córdoba, Argentina;8. Instituto de Fisica Enrique Gaviola, Consejo Nacional de Investigaciones Científicas y Técnicas, Medina Allende, Ciudad Universitaria, X5016LAE Córdoba, Argentina;1. Carbon Materials Research Group, Department of Inorganic Chemistry, Faculty of Sciences, University of Granada, Campus Fuentenueva s/n, 18071 Granada, Spain;2. Laboratory of Separation and Reaction Engineering – Laboratory of Catalysis and Materials (LSRE-LCM), Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal;3. Department of Precision and Microsystems Engineering, Research Group of Micro and Nano Engineering, Delft University of Technology, Mekelweg 2, 2628 CD Delft, The Netherlands
Abstract:An enantioselective high-performance liquid chromatographic method for the determination of E3810, a new anti-ulcer agent, in Beagle dog plasma and rat plasma has been developed. After extraction from plasma with ethyl acetate. E3810 enantiomer were measured by reversed-phase high-performance liquid chromatography on a Chiralcel OD-R column. The enantiomers were detected by ultraviolet absorbance detection at 290 nm. The recoveries of E3810 enantiomers and internal standard were greater than 91%. The calibration curves were linear from 0.03 to 20 μg/ml for Beagle dog plasma and from 0.1 to 100 μg/ml for rat plasma. The limits of quantification of both enantiomers were 0.03 μg/ml for Beagle dog plasma and 0.1 μg/ml for rat plasma. The intra- and inter-day accuracy and precision data showed good reproducibility of the method. The assay was applied for the analysis of E3810 enantiomers in plasma after intravenous administration of racemic E3810 to Beagle dogs and rats. This method should be very useful for enantioselective pharmacokinetic studies of E3810.
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