Lorenz S A, Maziarz E P, Wood T D
Department of Chemistry, State University of New York at Buffalo, 14260-3000, USA.
J Am Soc Mass Spectrom. 2001 Jul;12(7):795-804. doi: 10.1016/S1044-0305(01)00265-3.
Electrospray ionization (ESI) is a soft ionization technique that is able to transfer intact ions, as well as solution phase non-covalent complexes into the gas phase. With small molecules that have a high tendency to form hydrogen bonds, the observation of non-covalent complexes by ESI-MS can be the result of a non-specific interaction, due to the nature of the electrospray process. Special precautions and additional steps should be performed to identify the origin of the complexes observed with ESI-MS, and we have utilized solution phase hydrogen/deuterium (H/D) exchange as a method to determine the specificity of the complexes. By comparing the average number of exchanges for the monomer subunits to the average number of exchanges for the complex, one can distinguish if a specific complex is formed in solution. In this paper we have investigated non-covalent complexes of some common chemotherapy agents: paclitaxel, doxorubicin, and etoposide by ESI-MS. By using the solution phase H/D exchange, we were able to identify several specific drug-drug complexes. Thus, solution phase H/D exchange combined with ESI-MS provides for a convenient method in ascertaining the specificity of non-covalent complexes as being formed in solution or in vacuo.
电喷雾电离（ESI）是一种软电离技术，能够将完整离子以及溶液相非共价复合物转移到气相中。对于具有高形成氢键倾向的小分子，由于电喷雾过程的性质，通过ESI-MS观察到的非共价复合物可能是一种非特异性相互作用的结果。应采取特殊预防措施和额外步骤来确定通过ESI-MS观察到的复合物的来源，并且我们已利用溶液相氢/氘（H/D）交换作为确定复合物特异性的方法。通过比较单体亚基的平均交换数与复合物的平均交换数，可以区分溶液中是否形成了特定的复合物。在本文中，我们通过ESI-MS研究了一些常见化疗药物：紫杉醇、阿霉素和依托泊苷的非共价复合物。通过使用溶液相H/D交换，我们能够鉴定出几种特定的药物-药物复合物。因此，溶液相H/D交换与ESI-MS相结合为确定在溶液或真空中形成的非共价复合物的特异性提供了一种便捷方法。
