title: Microfluidic chip capillary electrophoresis coupled with electrochemiluminescence for enantioseparation of racemic drugs using central composite design optimization.
abstract: Optimization based on central composite design (CCD) for enantioseparation of anisodamine (AN), atenolol (AT), and metoprolol (ME) in human urine was developed using a microfluidic chip-CE device. Coupling the flexible and wide working range of microfluidic chip-CE device to CCD for chiral separation of AN, AT, and ME in human urine, a total of 15 experiments is needed for the optimization procedure as compared to 75 experiments using the normal one variable at a time optimization. The optimum conditions obtained are found to be more robust as shown by the curvature effects of the interaction factors. The developed microfluidic chip-CE-ECL system with adjustable dilution ratios has been validated by satisfactory recoveries (89.5-99% for six enanotiomers) in urine sample analysis. The working range (0.3-600 μM), repeatability (3.1-4.9% RSD for peak height and 4.0-5.2% RSD for peak area), and detection limit (0.3-0.6 μM) of the method developed are found to meet the requirements for bedside monitoring of AN, AT, and ME in patients under critical conditions. In summary, the hyphenation of CCD with the microfluidic chip-CE device is shown to offer a rapid means for optimizing the working conditions on simultaneous separation of three racemic drugs using the microfluidic chip-CE device developed.
authors.affiliation: Shenzhen Second People's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, P. R. China; Department of Chemistry, The University of Hong Kong, Hong Kong, P. R. China.
authors.forename: Wen Peng
authors.initials: WP
authors.lastname: Guo
authors.forename: Zhi Bin
authors.initials: ZB
authors.lastname: Rong
authors.forename: Ying Hong
authors.initials: YH
authors.lastname: Li
authors.forename: Ying Sing
authors.initials: YS
authors.lastname: Fung
authors.forename: Guo Quan
authors.initials: GQ
authors.lastname: Gao
authors.forename: Zhi Ming
authors.initials: ZM
authors.lastname: Cai
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000302:isolation & purification / Q000652:urine*; D001262:Atenolol / Q000302:isolation & purification / Q000652:urine*; D046209:Electrophoresis, Microchip / Q000295:instrumentation*; D004867:Equipment Design; D006801:Humans; D057230:Limit of Detection; D008163:Luminescent Measurements / Q000295:instrumentation; D008790:Metoprolol / Q000302:isolation & purification / Q000652:urine*; D015203:Reproducibility of Results; D012991:Solanaceous Alkaloids / Q000302:isolation & purification / Q000652:urine*; D013237:Stereoisomerism
chemical_list: D000889:Anti-Arrhythmia Agents; D012991:Solanaceous Alkaloids; C003922:anisodamine; D001262:Atenolol; D008790:Metoprolol
keywords: Central composite design; Enantioseparation; Ferrofluid valve; Microchip-CE; Spiral channel