Foltz David J, Castro-Perez Jose, Riley Pamela, Entwisle John R, Baker Timothy R
Procter & Gamble Pharmaceuticals, Health Care Research Center, 8700 Mason-Montgomery Road, Mason, OH 45040-8006, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Oct 25;825(2):144-51. doi: 10.1016/j.jchromb.2005.03.040. Epub 2005 Apr 18.
The identification of in vitro and in vivo metabolites is vital to the discovery and development of new pharmaceutical therapies. Analytical strategies to identify metabolites at different stages of this process vary, but all involve the use of liquid chromatography separations combined with detection via mass spectrometry (HPLC/MS). Reported here is the use of narrow-bore column (0.5-1.0 mm i.d.) trapping of metabolites, followed by back-flushing onto a matching analytical column. Separated metabolites were then identified using quadrupole time-of-flight mass spectrometry (MS) and tandem MS. Metabolites in human plasma and from low-level in vitro incubations, that were not identified using standard HPLC/MS approaches, were characterized using the instrumental configuration described here.
体外和体内代谢物的鉴定对于新药物疗法的发现和开发至关重要。在此过程不同阶段鉴定代谢物的分析策略各不相同,但都涉及使用液相色谱分离并结合质谱检测(HPLC/MS)。本文报道了使用窄内径柱(内径0.5 - 1.0 mm)捕集代谢物,然后反冲至匹配的分析柱上。然后使用四极杆飞行时间质谱(MS)和串联质谱鉴定分离出的代谢物。使用本文所述的仪器配置对人血浆中和低水平体外孵育中未通过标准HPLC/MS方法鉴定的代谢物进行了表征。