title: Quantitative determination of isoniazid in biological samples by cation-selective exhaustive injection-sweeping-micellar electrokinetic chromatography.
abstract: Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis, infects approximately one third of the current world population. Isoniazid is one of the most frequently used first-line anti-TB drugs. In this study, we developed a sensitive cation-selective exhaustive injection-sweeping-micellar electrokinetic chromatography method (CSEI-Sweep-MEKC) for analyzing isoniazid in human plasma. Parameters including acetonitrile (ACN) percentage in the separation buffer; the injection time, and concentration of the high-conductivity buffer; sodium dodecyl sulfate (SDS) concentration; phosphate concentration in the sample matrix; and the sample injection time were all optimized to obtain the best analytical performance. The optimal background electrolyte comprised 50 mM phosphate buffer, 100 mM SDS, and 15% ACN. Non-micelle background electrolyte, containing 75 mM phosphate buffer and 15% ACN, was first injected into the capillary, followed by a short plug of 200 mM phosphate (high-conductivity buffer). Run-to-run repeatability (n=3) and intermediate precision (n=3) of peak area ratios were found to be lower than 8.7% and 11.4% RSD, respectively. The accuracy of the method was within 98.1-106.9%. The limit of detection of isoniazod in human plasma was 9 ng mL(-1). Compared with conventional MEKC, the enhancement factor of the CSEI-Sweep-MEKC method was 85 in plasma samples. The developed method was successfully used to determine isoniazid concentration in patient plasma. The results demonstrated that CSEI-Sweep-MEKC has the potential to analyze isoniazid in human plasma for therapeutic drug monitoring and clinical research.
authors.affiliation: School of Pharmacy, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 100, Taiwan.
authors.forename: I-Lin
authors.initials: IL
authors.lastname: Tsai
authors.forename: Hsiang-Yin
authors.initials: HY
authors.lastname: Liu
authors.forename: Ping-Hung
authors.initials: PH
authors.lastname: Kuo
authors.forename: Jann-Yuan
authors.initials: JY
authors.lastname: Wang
authors.forename: Li-Jiuan
authors.initials: LJ
authors.lastname: Shen
authors.forename: Ching-Hua
authors.initials: CH
authors.lastname: Kuo
mesh_terms: D000097:Acetonitriles / Q000378:metabolism; D000995:Antitubercular Agents / Q000032:analysis*; D002021:Buffers; D002412:Cations / Q000737:chemistry*; D020374:Chromatography, Micellar Electrokinetic Capillary; D006801:Humans; D007538:Isoniazid / Q000032:analysis*; D008823:Micelles; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry
chemical_list: D000097:Acetonitriles; D000995:Antitubercular Agents; D002021:Buffers; D002412:Cations; D008823:Micelles; D012967:Sodium Dodecyl Sulfate; D007538:Isoniazid; C032159:acetonitrile