Hatsis Panos, Brockman Adam H, Wu Jing-Tao
Department of Drug Metabolism and Pharmacokinetics, Millennium Pharmaceuticals, Inc., 35 Landsdowne St, Cambridge, MA 02139, USA.
Rapid Commun Mass Spectrom. 2007;21(14):2295-300. doi: 10.1002/rcm.3093.
The potential of high-field asymmetric waveform ion mobility spectrometry (FAIMS) coupled to nanoelectrospray ionization (nanoESI) as a method to improve sample throughput for bioanalysis in a discovery pharmaceutical setting was explored in this work. The ability of FAIMS to separate gas-phase ions in the millisecond timescale was exploited to eliminate the need for liquid chromatography. Samples were introduced into the FAIMS electrodes/mass spectrometer using offline nanoESI at 20 nL/min and 1.5 kV. Signals were averaged for 30 s after which the next sample could be analyzed. The separation of simple mixtures, e.g., the removal of metabolite and endogenous interferences from parent drug, was demonstrated. Moreover, the application of nanoESI attenuated the ion suppression effects that normally plague conventional electrospray. On average, approximately two-thirds of the neat sample signal intensity was preserved in extracted plasma samples. Standard curves were prepared for several compounds and linearity was obtained over approximately two to three orders of magnitude. This methodology was further tested with the analysis of plasma samples from a mouse pharmacokinetic study. Concentration values determined using nanoESI-FAIMS were comparable to those determined using conventional LC/MS as demonstrated by percent differences of less than 30%. This work demonstrated the proof of concept that the combination of FAIMS and nanospray ionization can be a potentially useful tool to improve the throughput of discovery bioanalysis.
本研究探索了将高场不对称波形离子迁移谱（FAIMS）与纳米电喷雾电离（nanoESI）联用，作为在药物研发环境中提高生物分析样品通量的一种方法的潜力。利用FAIMS在毫秒级时间尺度内分离气相离子的能力，无需使用液相色谱。使用离线纳米电喷雾，以20 nL/分钟和1.5 kV的条件将样品引入FAIMS电极/质谱仪。信号平均采集30秒后即可分析下一个样品。展示了简单混合物的分离，例如从母体药物中去除代谢物和内源性干扰物。此外，纳米电喷雾电离的应用减弱了通常困扰传统电喷雾的离子抑制效应。平均而言，在提取的血浆样品中，约三分之二的纯样品信号强度得以保留。针对几种化合物制备了标准曲线，并在大约两到三个数量级范围内获得了线性关系。通过对小鼠药代动力学研究的血浆样品分析，进一步测试了该方法。使用纳米电喷雾电离 - FAIMS测定的浓度值与使用传统液相色谱/质谱测定的值相当，百分比差异小于30%即证明了这一点。这项工作证明了FAIMS和纳米喷雾电离相结合可能是提高药物研发生物分析通量的一种潜在有用工具的概念验证。
