Differential Mobility Spectrometry-Tandem Mass Spectrometry with Multiple Ion Monitoring Coupled with in Source-Collision Induced Dissociation: A New Strategy for the Quantitative Analysis of Pharmaceutical Polymer Excipients in Rat Plasma

Abstract

Polylactic acids (PLAs) are synthetic polymers composed of repeating lactic acid subunits. For their good biocompatibility, PLAs have been approved and widely applied as pharmaceutical excipients and scaffold materials. Liquid chromatography-tandem mass spectrometry is a powerful analytical tool not only for pharmaceutical ingredients but also for pharmaceutical excipients. However, the characterization of PLAs presents particular problems for mass spectrometry techniques. In addition to their high molecular weights and wide polydispersity, multiple charging and various adductions are intrinsic features of electrospray ionization. In the present study, a strategy combining of differential mobility spectrometry (DMS), multiple ion monitoring (MIM) and in-source collision-induced dissociation (in source-CID) has been developed and applied to the characterization and quantitation of PLAs in rat plasma. First, PLAs will be fragmented into characteristic fragment ions under high declustering potential in the ionization source. The specific fragment ions are then screened twice by quadrupoles to ensure a high signal intensity and low interference for mass spectrometry detection. Subsequently, DMS technique has been applied to further reduce the background noise. The appropriately chosen surrogate specific precursor ions could be utilized for the qualitative and quantitative analysis of PLAs, which provided results with the advantages of low endogenous interference, sufficient sensitivity and selectivity for bioassay. The linearity of the method was evaluated over the concentration range 3–100 μg/mL (r2 = 0.996) for PLA 20,000. The LC-DMS-MIM coupled with in source-CID strategy may contribute to the pharmaceutical studies of PLAs and the possible prospects of other pharmaceutical excipients.

Keywords

• differential mobility spectrometry
• multiple ion monitoring
• polylactic acids
• quantitative analysis
• pharmaceutical polymer excipients