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High-performance liquid chromatographic analysis of the tyrphostin AG1478, a specific inhibitor of the epidermal growth factor receptor tyrosine kinase,in mouse plasma
Institution:1. Pharmacology and Developmental Therapeutics Unit, Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, Locked Bag 1, A’Beckett Street, Melbourne, Victoria 8006, Australia;2. Epithelial Biochemistry Laboratory, Ludwig Institute for Cancer Research, P.O. Box 2008 RMH, Melbourne, Victoria 3050, Australia;3. Department of Biological Chemistry, Alexander Silverman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel;1. Division of Gastroenterology & Hepatology, Department of Medicine, University of Colorado, School of Medicine, 12631 E. 17th Avenue, MS B-158, Aurora, CO 80045, USA;2. University of Colorado, School of Medicine, 12631 E. 17th Avenue, MS B-158, Aurora, CO 80045, USA;1. Université Paris-Saclay, Institut Gustave-Roussy, département de cancérologie de l’enfant et de l’adolescent, 114, rue Édouard-Vaillant, 94800 Villejuif, France;2. Centre Oscar-Lambret, département de radiothérapie, 3, rue Frédéric-Combemale, 59000 Lille, France;3. Institut Curie, département d’oncologie médicale, 26, rue d’Ulm, 75005 Paris, France;4. AP–HP, hôpitaux universitaires Paris Sud, hôpital Bicêtre, département de chirurgie pédiatrique, 78, rue du Général-Leclerc, 94270 Le Kremlin-Bicêtre, France;5. AP–HP, groupe hospitalier Pitié-Salpêtrière, hôpital La Pitié-Salpétrière, UF d’oncogénétique et d’angiogénétique, 47-83, boulevard de l’Hôpital, 75013 Paris, France;6. CHU Pellegrin, service de chirurgie gynécologique, place Amélie-Raba-Léon, 33076 Bordeaux, France;7. Université Paul-Sabatier Toulouse III, 118, route de Narbonne, 31062 Toulouse, France;8. Institut universitaire du cancer de Toulouse–Oncopole, avenue Hubert-Curien, 31100 Toulouse, France;9. Fondation Adolphe-de-Rothschild, ENT and cervico-facial surgery department, 29, rue Manin, 75019 Paris, France;10. Institut Curie, département de pédiatrie – adolescents–jeunes adultes, Groupe français « FRACTURE » des tumeurs rares de l’enfant de la Société française des cancers de l’enfant (SFCE), 26, rue d’Ulm, 75005 Paris, France;11. Université Paris-Saclay, Institut Gustave-Roussy, U1018, centre d’épidémiologie et de santé des populations (CESP), Institut national de la santé et de la recherche médicale (Inserm), 114, rue Édouard-Vaillant, 94800 Villejuif, France;1. Department of Thyroid and Breast Surgery, The 960th Hospital of PLA, Jinan, 250031, China;2. Department of Oncology, The 960th Hospital of PLA, Jinan, 250031, China;3. Department of Pathology, The 960th Hospital of PLA, Jinan, 250031, China;1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Ain Helwan 11795, Cairo, Egypt;2. Department of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA;3. Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Centre for Scientific Research “Demokritos”, Athens, Greece;4. Department of Pharmacology, School of Medicine, University of Crete, Voutes, 71003, Heraklion, Crete, Greece;5. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The British University in Egypt (BUE), El-Sherouk City, Suez Desert Road, Cairo 11837, Egypt;6. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia 11566, Cairo, Egypt;7. Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, Egypt;8. Basic and Applied Sciences Institute, Egypt-Japan University of Science and Technology (E-JUST), New Borg El-Arab City, 21934 Alexandria, Egypt;1. Department of Clinical Pharmacy and Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh;2. Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh;3. Pharmacogenetics Lab, Labaid Limited, Dhaka, Bangladesh;4. Department of Pharmacy, Noakhali Science and Technology University, Sonapur, Noakhali 3814, Bangladesh;1. Cancer Metastasis Alert and Prevention Center, Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, and Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou, 350002, PR China;2. Science College of Hunan Agricultural University, Changsha 410128, PR China;3. Henan Key Laboratory of Immunology and Targeted Drugs, Research Center for Molecular Oncology and Functional Nucleic Acids, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, PR China
Abstract:The tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyquinazoline (AG1478) is undergoing evaluation as a potential new anticancer agent. We have developed a specific and sensitive reversed-phase HPLC assay for AG1478 in mouse plasma. The method involves a rapid and simple extraction process followed by separation on a Symmetry C8 stationary phase with a gradient of acetonitrile in ammonium acetate buffer. A linear response was achieved over the concentration range of 0.2–100 μM using multilevel calibration with internal standard method of calculation. Inter- and intra-assay accuracy and precision were better than ±10%. The limit of quantitation was 0.2 μM. We have used this method to study the preclinical pharmacokinetics of this new agent in mice.
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