Department of Drug Metabolism and Pharmacokinetics, Millennium Pharmaceuticals Inc., 35 Landsdowne St, Cambridge, MA 02139, USA.
Rapid Commun Mass Spectrom. 2009 Dec;23(23):3736-42. doi: 10.1002/rcm.4311.
Nanoelectrospray ionization (nESI) coupled online with high-field asymmetric waveform ion mobility spectrometry (FAIMS) for small molecule analysis in a discovery pharmaceutical setting was examined. A conventional capillary pump, autosampler and nESI source were used to introduce samples directly into the FAIMS device. The FAIMS device was used to separate gas-phase ions on a timescale that was compatible with the mass spectrometer. The capability of the nESI-FAIMS combination to efficiently remove metabolite interferences from the parent drug, and reduce ion suppression effects, was demonstrated. On average, 85% of the signal intensity obtained from a neat sample was preserved in the extracted plasma samples. Standard curves were prepared for several compounds. Linearity was obtained over approximately 3 to 4 orders of magnitude. Comparison of results from nESI-FAIMS with those from conventional LC/MS for a mouse pharmacokinetic study yielded concentration values differing by no more than 30%.
在发现药物环境中，对与纳米电喷雾电离（nESI）与高场非对称波形离子迁移谱（FAIMS）在线联用进行小分子分析进行了考察。采用常规毛细管泵、自动进样器和 nESI 源将样品直接引入 FAIMS 装置。FAIMS 装置用于在与质谱仪兼容的时间尺度上分离气相离子。结果表明，nESI-FAIMS 联用能够有效地去除母体药物中的代谢物干扰，并减少离子抑制效应。平均而言，从纯样品获得的信号强度的 85%在提取的血浆样品中得以保留。对几种化合物进行了标准曲线的制备。在大约 3 到 4 个数量级范围内获得了线性关系。对小鼠药代动力学研究中 nESI-FAIMS 与常规 LC/MS 结果的比较表明，浓度值差异不超过 30%。
