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. 2023 Jun 15;28(12):4782.
doi: 10.3390/molecules28124782.

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

Yuyao Zhang  1   2 , Zhi Zhang  1 , Yingze Liu  1 , Deqi Cai  1   2 , Jingkai Gu  1   2 , Dong Sun  1
Affiliations

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

Yuyao Zhang et al. Molecules. .

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; pharmaceutical polymer excipients; polylactic acids; quantitative analysis.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
MS scanning result for PLA 20,000 using in source-CID. Different series ions were observed, including [M + H]+ series ions (m/z 217.1, 289.3, 361.3, 433.2 and 505.4), [M + Na]+ series ions (m/z 455.2, 527.1, 599.3, 671.2, 743.2, 815.4 and 887.4) and [M + K]+ (m/z 615.3, 687.4 and 759.4) were observed.
Figure 2
Figure 2
MS2 scanning result for PLA 20,000 under CE 80 eV. Precursor ion m/z 671.2 still had high MS intensity and fragment ions produced by m/z 671.2 was not stable with low intensity under such fragment condition. The result showed the poor fragmentation efficiency of PLA 20,000.
Figure 3
Figure 3
Optimization of SV and COV of PLA 20,000. The result showed under the conditions of SV 3500 V and COV 6.00 V obtained the highest MS intensity.
Figure 4
Figure 4
Optimization of DR of PLA 20,000. Figures showed chromatograms under different DR settings and at “medium” setting obtained the highest S/N of chromatographic peak.
Figure 5
Figure 5
Chromatography of PLA 20,000 at LLOQ concentration (3 μg/mL) under LC-DMS-MIM, LC-MRM and LC-MIM scanning modes. With the comparation between these modes, LC-DMS-MIM showed the best separation effect of PLA 20,000 from interference and background noise in plasma matrix.
Figure 6
Figure 6
Chromatography of different ions of PLA 20,000 under LC-DMS-MIM mode with in source-CID, including [7 LA + Na]+, [8 LA + Na]+, [9 LA + Na]+ and [10 LA + Na]+. Among these four surrogate precursor ions, [9 LA + Na] (m/z = 671.2) showed the highest intensity and S/N.
Figure 7
Figure 7
Chromatography of matrix blank and LLOQ samples of PLA 20,000 and IS.
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