An effective pretreatment technique based on multi-walled carbon nanotubes to reduce the matrix effect in plasma samples analyzed by a new type probe electrospray ionization method

The quantitative analysis of drug plasma samples plays an important role in the drug development and drug clinical use. Our research team developed a new electrospray ion source-Micro probe electrospray ionization (mu PESI) in the early stage, which was combined with mass spectrometry (mu PESI-MS/MS) showing good qualitative and quantitative analysis performance. However, matrix effect severely interfered the sensitivity in mu PESI-MS/MS analysis. To solve this problem, we recently developed a Solid-phase purification method based on multi-walled carbon nanotubes (MWCNTs), which was used for removing matrix interfering substances (especially phospholipid compounds) in the preparation of plasma samples, so as to reduce the matrix effect. In this study, aripiprazole (APZ), carbamazepine (CBZ) and omeprazole (OME) were used as representative analytes, the quantitative analysis related to the plasma samples spiked with the analytes above and the mechanism of the MWCNTs to reduce matrix effect were both investigated. Compared with the ordinary protein precipitation, MWCNTs could reduced the matrix effect for several to dozens of times, which resulting from the removement of phospholipid compounds from the plasma samples by MWCNTs in the selective adsorption manner. We further validated the linearity, precision and accuracy of this pretreatment technique by the mu PESI-MS/MS method. These parameters all met the requirements of FDA guidelines. It was showed that MWCNTs have a good application prospect in the drug quantitative analysis of plasma samples using the mu PESI-ESI-MS/MS method.