title: Development and validation of an HPLC method for quantitation of BA-TPQ, a novel iminoquinone anticancer agent, and an initial pharmacokinetic study in mice.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Al 35294, USA.
authors.forename: Haibo
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Al 35294, USA.
authors.forename: Scharri J
authors.initials: SJ
authors.lastname: Ezell
authors.affiliation: Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Al 35294, USA.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Al 35294, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Al 35294, USA.|College of Preventive Medicine, The Third Military Medical University, Chongqing 400038, P. R. China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Al 35294, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Rayburn
authors.affiliation: Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Al 35294, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Al 35294, USA.
authors.forename: Evrim
authors.initials: E
authors.lastname: Gurpinar
authors.affiliation: Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Al 35294, USA.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Al 35294, USA.
authors.forename: Charnell I
authors.initials: CI
authors.lastname: Sommers
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham, Birmingham, Al 35294, USA.|Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Al 35294, USA.
authors.forename: Sadanandan E
authors.initials: SE
authors.lastname: Velu
authors.affiliation: Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Al 35294, USA.|Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Al 35294, USA.
authors.forename: Ruiwen
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016018:Least-Squares Analysis; D008297:Male; D051379:Mice; D011758:Pyrroles / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics*; D015363:Quinolones / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: C553817:7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one; D000970:Antineoplastic Agents; D011758:Pyrroles; D015363:Quinolones