Deng Yuzhong, Zhang Hongwei, Wu Jing-Tao, Olah Timothy V
PCO, Bristol-Myers Squibb Company, P.O. Box 4000, Princeton, NJ 85430, USA.
Rapid Commun Mass Spectrom. 2005;19(20):2929-34. doi: 10.1002/rcm.2144.
In this work, high-flow online reversed-phase extraction was coupled with normal phase on silica columns with aqueous-organic mobile phase liquid chromatography/tandem mass spectrometry (LC/MS/MS) to quantify drug candidates in biological fluids. The orthogonal separation effect obtained from this configuration considerably reduced matrix effects and increased sensitivity for highly polar compounds as detected by selected reaction monitoring. This approach also significantly improved the robustness and limit of detection of the assays. An evaluation of this system was performed using a mixture of albuterol and bamethan in rat plasma. Assay validation demonstrated acceptable accuracy (< 8% difference) and precision (< 6% CV) for these model compounds. The system has been used for the quantitation of polar ionic compounds in biological fluids in support of drug discovery programs. This assay was used to analyze samples for a BMS proprietary compound (A) in a rat pharmacokinetic study and is shown as an example to demonstrate the precision, accuracy, and sufficient sensitivity of this system.
在本研究中，高流量在线反相萃取与硅胶柱上的正相萃取相结合，并采用水-有机流动相液相色谱/串联质谱（LC/MS/MS）技术对生物流体中的候选药物进行定量分析。通过这种配置获得的正交分离效果显著降低了基质效应，并提高了通过选择反应监测检测到的高极性化合物的灵敏度。该方法还显著提高了分析方法的稳健性和检测限。使用沙丁胺醇和巴美生的混合物对大鼠血浆进行了该系统的评估。分析方法验证表明，这些模型化合物的准确度（差异<8%）和精密度（CV<6%）可接受。该系统已用于支持药物发现计划的生物流体中极性离子化合物的定量分析。在一项大鼠药代动力学研究中，该分析方法用于分析BMS专有化合物（A）的样品，并作为示例展示了该系统的精密度、准确度和足够的灵敏度。
