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Development and validation of an HPLC method for quantitation of BA‐TPQ, a novel iminoquinone anticancer agent, and an initial pharmacokinetic study in mice
Author(s) -
Li Haibo,
Ezell Scharri J.,
Zhang Xiangrong,
Wang Wei,
Xu Hongxia,
Rayburn Elizabeth R.,
Zhang Xu,
Gurpinar Evrim,
Yang Xinyi,
Sommers Charnell I.,
Velu Sadanandan E.,
Zhang Ruiwen
Publication year - 2011
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.1498
Subject(s) - chromatography , chemistry , pharmacokinetics , high performance liquid chromatography , acetonitrile , extraction (chemistry) , ethyl acetate , pharmacology , biology
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 C 18 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.