Klaassen Tobias, Szwandt Simon, Kapron James T, Roemer Axel
A&M Labor für Analytik und Metabolismusforschung Service GmbH, Kopernikusstrasse 25, 50126 Bergheim, Germany.
Rapid Commun Mass Spectrom. 2009 Aug;23(15):2301-6. doi: 10.1002/rcm.4147.
The analysis of peptides presents serious challenges for bioanalytical scientists including low total ion current and non-selective fragmentation during tandem mass spectrometry (MS/MS). During method validation of a peptide in rat serum matrix some interferences could not be easily removed and thus prevented accurate and precise measurement. These problems associated with peptide quantitation were resolved by using FAIMS (high-Field Asymmetric waveform Ion Mobility Spectrometry). This selectivity-enhancing technique filters out matrix interferences, and the resulting pseudo-selected reaction monitoring (pseudo-SRM) chromatograms were nearly free from interferences. Control blank matrix samples contained an acceptable level of interference (only 7% signal as compared to the lower level of quantitation). Chromatographic peaks were easily, accurately and precisely integrated resulting in a validated liquid chromatography (LC)/FAIMS-MS/MS method for the analysis of a peptide drug in rat serum according to United States Food and Drug Administration (US FDA) bioanalytical guidelines. These results confirm that new selectivity-enhancing technologies aid the pharmaceutical industry in reliably producing acceptable pharmacokinetic data.
对肽段进行分析给生物分析科学家带来了严峻挑战，包括串联质谱（MS/MS）过程中总离子流较低以及非选择性裂解。在对大鼠血清基质中的一种肽段进行方法验证时，一些干扰难以轻易去除，从而妨碍了准确且精确的测量。通过使用FAIMS（高场不对称波形离子迁移谱）解决了与肽段定量相关的这些问题。这种增强选择性的技术滤除了基质干扰，所得的伪选择反应监测（pseudo-SRM）色谱图几乎没有干扰。对照空白基质样品的干扰水平可接受（与较低定量水平相比，信号仅为7%）。色谱峰易于、准确且精确地积分，从而产生了一种根据美国食品药品监督管理局（US FDA）生物分析指南对大鼠血清中一种肽类药物进行分析的经过验证的液相色谱（LC）/FAIMS-MS/MS方法。这些结果证实，新的增强选择性技术有助于制药行业可靠地生成可接受的药代动力学数据。
