title: A novel two-dimensional liquid chromatographic system for the online toxicity prediction of pharmaceuticals and related substances.
abstract: In this study, a novel two-dimensional liquid chromatographic (2D-LC) system was developed for simultaneous separation and toxicity prediction of pharmaceutical and its related substances. A conventional ODS column was used on the 1st-D to separate the sample; while, bio-partitioning micellar chromatography served as the 2nd-D to predict toxicity of the components. The established system was tested for the toxicity of ibuprofen and its impurities with known toxicity. With only one injection, ibuprofen and its impurities were separated on the 1st-D; and LC50 values of individual impurity were obtained based on the quantitative retention-activity relationships, which agreed well with the reported data. Furthermore, LC50 values of photolysis transformation products (TPs) of carprofen, ketoprofen and diclofenac acid (as unknown compounds) were screened in this 2D-LC system, which could be an indicator of the toxicity of these TPs and was meaningful for the environmental monitoring and drinking water treatment. The established 2D-LC system was cost-effective, time-saving and reliable, and was promising for fast online screening of toxicity of known and unknown analytes in the complex sample in a single step. It may find applications in environment, pharmaceutical and food, etc.
authors: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Jian
authors: J
authors: Li
authors: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Li
authors: L
authors: Xu
authors: Department of Chemistry, Wuhan University, Wuhan 430072, China. Electronic address: shizg@whu.edu.cn.
authors: Zhi-guo
authors: ZG
authors: Shi
authors: Hubei Instrument for Food and Drug Control, Wuhan, China.
authors: Min
authors: M
authors: Hu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000633:toxicity*; D002227:Carbazoles / Q000737:chemistry / Q000633:toxicity; D000460:Chlorophyta / Q000187:drug effects; D002853:Chromatography, Liquid / Q000379:methods; D003198:Computer Simulation; D003621:Daphnia / Q000187:drug effects; D004008:Diclofenac / Q000737:chemistry / Q000633:toxicity; D004340:Drug Contamination; D064420:Drug-Related Side Effects and Adverse Reactions; D005399:Fishes; D007052:Ibuprofen / Q000737:chemistry / Q000633:toxicity; D007660:Ketoprofen / Q000737:chemistry / Q000633:toxicity; D007928:Lethal Dose 50; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010782:Photolysis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D004364:Pharmaceutical Preparations; D004008:Diclofenac; D007660:Ketoprofen; C007005:carprofen; D007052:Ibuprofen
keywords: Biochromatography; Toxicity prediction; Two-dimensional liquid chromatography