title: Ultra-high capacity liquid chromatography chip/quadrupole time-of-flight mass spectrometry for pharmaceutical analysis.
abstract: Nanoflow liquid chromatography/mass spectrometry (nano-LC/MS) has attracted increasing interest in virtue of high sensitivity, low sample consumption, and minimal matrix effect. In this work a HPLC-Chip/quadrupole time-of-flight (Q-TOF) MS device with a new ultra-high capacity small molecule chip (UHC-Chip) which features a 500 nL enrichment column and a 150 mm × 75 μm analytical column, was evaluated with a drug mixture covering a wide range of polarities. Excellent chromatographic precision with 0.1-0.5% RSD for retention time and 1.7-9.0% RSD for peak area, low limit of detection, good chip-to-chip reproducibility and linearity were obtained by using this UHC-Chip. Compared with the standard HPLC-Chip with 40 nL trapping column, the UHC-Chip showed higher enrichment capability and hence gave a higher response in signal detection. Additionally, 4-30 times increase in sensitivity was obtained compared with conventional LC/MS, which indicated that UHC-Chip/MS was a valuable tool for the quantitative analysis of low level impurities and degradation products in pharmaceuticals. Moreover, satisfactory results obtained from trace drug analysis of serum samples further proved its practicality and potential for use in drug testing and development.
authors.affiliation: CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian 116023, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Zhao
authors.forename: Zeming
authors.initials: Z
authors.lastname: Wu
authors.forename: Gang
authors.initials: G
authors.lastname: Xue
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Yining
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zhixiu
authors.initials: Z
authors.lastname: Xu
authors.forename: Dayin
authors.initials: D
authors.lastname: Lin
authors.forename: Godel
authors.initials: G
authors.lastname: Herbert
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Chang
authors.forename: Kaiyang
authors.initials: K
authors.lastname: Cai
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
mesh_terms: D000818:Animals; D053801:Capillary Electrochromatography / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007099:Imipramine / Q000097:blood; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000097:blood / Q000302:isolation & purification; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D004364:Pharmaceutical Preparations; D007099:Imipramine