Quantitative Analysis of Dichloromethylene-Bisphosphonic Acid in Human Plasma by Nanoprobe Based Affinity Mass Spectrometry

摘要

Clodronate, belonging to bisphosphonates drug, is used in treatment of various bone disease. In pharmacokinetic studies, many researches have been reported for metabolism of clodronate in human biofluid. However, these conventional sample pretreatment methods such as precipitation and solid /liquid phase extraction usually required derivation method that is tedious and time-consuming. By the high affinity between the bisphophonate group and transition metal ion, we reported a magnetic metal-chelating ligand by covalent conjugation of nitrilotriactic acid (NTA) on the magnetic nanoparticle (MNP) for simultaneous enrichment and detection of clodronate, as shown in Figure 1. Without the need of sample derivation and elution, the magnetic NTA nanoparticle demonstrated an efficient metal chelated probe compatible to MALDI MS analysis. Rapid isolation of low abundance of clodronate from the human plasma can be achieved.