Development and validation of an HPLC method for quantitation of BA‐TPQ,a novel iminoquinone anticancer agent,and an initial pharmacokinetic study in mice |
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| Authors: | Wei Wang Hongxia Xu Elizabeth R. Rayburn Xu Zhang Evrim Gurpinar Xinyi Yang Charnell I. Sommers Sadanandan E. Velu Ruiwen Zhang |
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| Affiliation: | 1. Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;2. College of Preventive Medicine, The Third Military Medical University, Chongqing 400038, People's Republic of China;3. Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL 35294, USA;4. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA |
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| Abstract: | We herein describe the development and validation of an HPLC method for the quantitation of 7‐(benzylamino)‐1,3,4,8‐tetrahydropyrrolo [4,3,2‐de]quinolin‐8(1H)‐one (BA‐TPQ), a newly synthesized iminoquinone anticancer agent. BA‐TPQ was extracted from plasma and tissue samples by first precipitating proteins with acetonitrile followed by a liquid–liquid extraction with ethyl acetate. Chromatographic separation was carried out using a gradient flow rate on a Zorbax SB C18 column, and the effluent was monitored by UV detection at 346 nm. The method was found to be precise, accurate, and specific, with a linear range of 3.91–1955.0 ng/mL in plasma, 19.55–1955.0 ng/mL in spleen, brain, and liver homogenates and 19.55–3910.0 ng/mL in heart, lung and kidney homogenates. The method was stable under all relevant conditions. Using this method, we also carried out an initial study determining plasma pharmacokinetics and tissue distribution of BA‐TPQ in mice following intravenous administration. In summary, this simple and sensitive HPLC method can be used in future preclinical and clinical studies of BA‐TPQ. |
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| Keywords: | BA‐TPQ HPLC iminoquinone pharmacokinetics |
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