title: Development and validation of an HPLC-MS/MS analytical method for quantitative analysis of TCBA-TPQ, a novel anticancer makaluvamine analog, and application in a pharmacokinetic study in rats.
abstract: We have recently designed and synthesized several novel iminoquinone anticancer agents that have entered preclinical development for the treatment of human cancers. Herein we developed and validated a quantitative HPLC-MS/MS analytical method for one of the lead novel anticancer makaluvamine analog, TCBA-TPQ, and conducted a pharmacokinetic study in laboratory rats. Our results indicated that the HPLC-MS/MS method was precise, accurate, and specific. Using this method, we carried out in vitro and in vivo evaluations of the pharmacological properties of TCBA-TPQ and plasma pharmacokinetics in rats. Our results provide a basis for future preclinical and clinical development of this promising anticancer marine analog.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China; Center for Drug Evaluation, China Food and Drug Administration, Beijing 100038, China.
authors.forename: Jun-Xian
authors.initials: JX
authors.lastname: Yu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China; China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Sukesh
authors.initials: S
authors.lastname: Voruganti
authors.affiliation: Center for Drug Evaluation, China Food and Drug Administration, Beijing 100038, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Li
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China; China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jiang-Jiang
authors.initials: JJ
authors.lastname: Qin
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Subhasree
authors.initials: S
authors.lastname: Nag
authors.affiliation: China National Institutes for Food and Drug Control, Beijing 100035, China.
authors.forename: Su
authors.initials: S
authors.lastname: Xu
authors.affiliation: China National Institutes for Food and Drug Control, Beijing 100035, China.
authors.forename: Sadanandan E
authors.initials: SE
authors.lastname: Velu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China; China Pharmaceutical University, Nanjing 210009, China. Electronic address: wwei.wang@ttuhsc.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China; China Pharmaceutical University, Nanjing 210009, China. Electronic address: ruiwen.zhang@ttuhsc.edu.
authors.forename: Ruiwen
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D011758:Pyrroles / Q000097:blood / Q000493:pharmacokinetics*; D015363:Quinolones / Q000097:blood / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
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
keywords: LC-MS/MS; Makaluvamine analogs; Pharmacokinetics; Rat plasma; TCBA-TPQ