Preparation of Molecularly Imprinted Polymers for Promazines and Determination of Chlorpromazine and Its Metabolites in Rat Plasma by Column-Switching LC

Jun Haginaka, Mukogawa Womens University, Nishinomiya, Japan (haginaka@mukogawa-u.ac.jp)

Molecularly imprinted polymers (MIPs) could be utilized for selective extraction of a target compound and its structurally related compound(s) from complex matrices. One of their disadvantages is a leakage problem, where the leaked template molecule prevents the accurate and precise assay for a target compound. In order to overcome this problem, a structurally related analogue or a deuterated molecule (a dummy-template molecule) has been used to prepare MIPs. In this study, MIPs for chlorpromazine (CPZ) and bromopromazine (BPZ), MIP_CPZ and MIP_BPZ, were prepared using methacrylic acid as a functional monomer and ethylene glycol dimethacrylate as a crosslinker by multi-step swelling and polymerization. The retention and molecular-recognition ability of MIP_CPZ and MIP_BPZ was evaluated in reversed-phase LC. Each MIP recognized the template molecule the most, while CPZ metabolites, desmethyl CPZ (DM-CPZ), CPZ sulfoxide (CPZ-SO) and 7-hydroxy CPZ (7-OH-CPZ), were moderately recognized on MIP_CPZ and MIP_BPZ. Furthermore, both MIPs gave similar retention and molecular-recognition ability for CPZ and its metabolites. For avoiding the template-leakage problem, MIP_BPZ was used for the determination of CPZ and its metabolites in rat plasma samples as the pretreatment column in column-switching LC with UV detection. In addition to DM-CPZ and CPZ-SO, didesmethyl CPZ (DDM-CPZ) and CPZ N-oxide (CPZ-NO) were speculated as the metabolites in rat plasma after administration of CPZ using LC-ESI-TOF-MS, while 7-OH-CPZ was not detected as the metabolite. Finally, we validated the column-switching LC method and applied it to the determination of CPZ and its metabolites, DM-CPZ, DDM-CPZ, CPZ-SO and CPZ-NO, in rat plasma samples after intravenous or oral administration of CPZ. 

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Abstract Reference & Short Personal Biography of Presenting Author

Dr. Jun Haginaka is a pharmacist from Kyoto University, Kyoto, Japan with a PhD in pharmaceutical Sciences in 1982 from the same University. He promoted to Full Professor in 1994 at Mukogawa Womens University through Lecturer and Associate Professor. His research interests include analysis of drugs and their metabolites in biological fluids by chromatographic and electrophoretic methods; preparation and application of protein-based stationary phases; and preparation and application of molecularly imprinted polymers. He has published about 250 original research papers, 30 review articles and 30 book chapters, and has held 25 patents. As from 1 January 2002, he became an editor of Journal of Pharmaceutical and Biomedical Analysis. His awards include the Japan Society for Analytical Chemistry Award for Young Scientists, the Pharmaceutical Society of Japan Award for Young Scientists, the Society for Chromatographic Sciences Award, the Japan Society for Analytical Chemistry Award and the Molecular Chirality Award.