Ultrasensitive determination of underivatized adamantane analogs in biological fluids by capillary electrophoresis with contactless conductivity detection

• Published in: Microchemical journal Vol. 169; p. 106602
• Main Authors: Wang, Zheng Ren, Hsieh, Ming-Mu, Sung, Yi-Yang
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2021
• Subjects: Adamantane drugs; Body fluids; Capacitively coupled contactless conductivity detection; Capillary electrophoresis; Filed amplified sample stacking; Ultrasound-assisted dispersive liquid–liquid microextraction; Body fluids; C4D; Capillary electrophoresis; Adamantane drugs; Filed amplified sample stacking; FASS; Ultrasound-assisted dispersive liquid–liquid microextraction; DLLME; Capacitively coupled contactless conductivity detection
• ISSN: 0026-265X; 1095-9149
• DOI: 10.1016/j.microc.2021.106602

[Display omitted] •Good recoveries low LODs and interference-free electropherograms were obtained.•Elaborated technique was applied for human urine and serum samples analysis.•UA-DLLME and FASS in CE with C4D for the simultaneous analysis of three underivatized adamantane drugs.•Using this technique, 1300–1800-fold improvement in the sensitivity was obtained.•This technique provides simple, fast, cheap, biocompatible, underivatized sample and efficient method. Separation techniques are promising for the detection of adamantane analogs with various functional groups. The derivatization of adamantane analogs with chromophores or fluorophores should be conducted using a separation technique combined with a common ultraviolet–visible or fluorescence detector. However, limited research has been conducted on underivatized adamantane analogs. Therefore, we present a highly rapid and sensitive method for detecting underivatized adamantane analogs by integrating ultrasound-assisted dispersive liquid–liquid microextraction (UADLLME), field-amplified sample stacking (FASS)-related capillary electrophoresis (CE), and capacitively coupled contactless conductivity detection (C4D). In the proposed system, UADLLME is used for sample clean up and analyte enrichment, whereas FASS-related CE provides on-line concentration of underivatized adamantane analogs during CE separation. A mixture of memantine (MT), amantadine (AT), and rimantadine (RT) was separated at baseline within 8 min through the application of optimized UADLLME (mixing extraction solvent, 50 μL of 1,1,2,2-tetrachloroethane (C2H2Cl4) and dispersive solvent, 200 μL of acetonitrile; mixing solution was injected into 1 mL of the sample solution at pH 12.5), FASS (buffer, 1.5 M acetic acid; additive, 0.05 mM β-cyclodextrin; pH 2.5), and C4D (amplitude, 2 Vpp; frequency, 500 kHz). The calibration curve exhibited acceptable linearity, with a coefficient of determination higher than 0.99. The limits of detection (signal-to-noise ratio of 3) were estimated to be 0.9, 1.0, and 1.2 nM for MT, AT, and RT, respectively. The relative standard deviations of peak areas varied from 8.9% to 9.3% (n = 5), whereas the sensitivity improvement of three underivatized adamantane analogs ranged from 1342 to 1766. The feasibility and accuracy of the present method for the determination of MT, AT, and RT in human serum and urine was satisfactorily confirmed by the excellent recovery and relative error. The proposed method exhibited high enrichment factors and offers excellent precision, high accuracy, and a short analysis time.