Lam Wing, Ramanathan Ragu
Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Global Research and Development, Ann Arbor, Michigan 48105, USA.
J Am Soc Mass Spectrom. 2002 Apr;13(4):345-53. doi: 10.1016/S1044-0305(02)00346-X.
A new method is described for performing hydrogen/deuterium (H/D) exchange in an electrospray ionization (ESI) source. The use of liquid chromatography (LC)-mass spectrometer equipped with an ESI source and deuterium oxide (D2O) as the sheath liquid allows H/D exchange experiments to be performed on-line. This directly provides information for determining the number and position of exchangeable hydrogens, aiding in the elucidation of the structures of drug metabolites. To demonstrate the utility of this method, LC-mass spectrometry (MS) and LC-MS/MS experiments were performed using either H2O or D2O as sheath liquid on a matrix metalloprotease (MMP) inhibitor (PD 0200126) and its metabolites. Examination of the mass shift of the deuteriated molecule from that of the protonated molecule allowed the number of exchangeable protons to be determined. Interpretation of the production-spectra helped to determine the location of the exchanged protons and assisted in the assignment of the site(s) of modification for each metabolite.
本文描述了一种在电喷雾电离（ESI）源中进行氢/氘（H/D）交换的新方法。使用配备ESI源和氧化氘（D2O）作为鞘液的液相色谱（LC）-质谱仪，可在线进行H/D交换实验。这直接为确定可交换氢的数量和位置提供了信息，有助于阐明药物代谢物的结构。为证明该方法的实用性，以水（H2O）或氧化氘（D2O）作为鞘液，对基质金属蛋白酶（MMP）抑制剂（PD 0200126）及其代谢物进行了LC-质谱（MS）和LC-MS/MS实验。通过检查氘化分子相对于质子化分子的质量位移，可确定可交换质子的数量。产物光谱的解释有助于确定交换质子的位置，并辅助确定每种代谢物的修饰位点。
