Reactive Desorption Electrospray Ionization Mass Spectrometry To Determine Intrinsic Degradability of Poly(lactic-co-glycolic acid) Chains

Abstract

Because of its speed, sensitivity, and ability to scrutinize individual species, mass spectrometry (MS) has become an essential tool in analytical strategies aimed at studying the degradation behavior of polyesters. MS analyses can be performed prior to the degradation event for structural characterization of initial substrates or after it has occurred to measure the decreasing size of products as a function of time. Here, we show that MS can also be usefully employed during the degradation process by online monitoring the chain solvolysis induced by reactive desorption electrospray ionization (DESI). Cleavage of ester bonds in random copolymers of lactic acid (LA) and glycolic acid (GA) was achieved by electrospraying methanol-containing NaOH onto the substrates. Experimental conditions were optimized to generate methanolysis products of high abundance so that mass spectra can be conveniently processed using Kendrick-based approaches. The same reactive-DESI performance was demonstrated for two sample preparations, solvent casting for soluble samples or pressed pellets for highly crystalline substrates, permitting to compare polymers with LA/GA ratios ranging from 100/0 to 5/95. Analysis of sample fractions collected by size exclusion chromatography showed that methanolysis occurs independently of the original chain size, so data recorded for poly(LA-co-GA) (PLAGA) copolymers with the average molecular weight ranging from 10 to 180 kDa could be safely compared. The average mass of methanolysis products was observed to decrease linearly (R 2 = 0.9900) as the GA content increases in PLAGA substrates, consistent with the susceptibility of ester bonds toward solvolysis being higher in GA than in LA. Because DESI only explores the surface of solids, these data do not reflect bulk degradability of the copolymers but, instead, their relative degradability at the molecular level. Based on a "reactive-DESI degradability scale" such as that established here for PLAGA, the proposed method offers interesting perspectives to qualify intrinsic degradability of different polyesters and evaluate their erosion susceptibility or to determine the degradability of those polymers known to degrade via erosion only.

Mass spectrometry of polymers: A tutorial review

“…Reactive DESI has been shown to overcome the sensitivity issues encountered in traditional DESI‐MS, thus increasing this method's robustness as an analytical tool. The reactive DESI process has been successfully applied to detect and characterize fatty acids, algae extracts, and polymers (Fouquet et al, 2021; Nyadong et al, 2009).…”

Applications of ambient ionization mass spectrometry in 2021: An annual review

“…Fouquet et al. applied reactive‐DESI to perform online monitoring of chain solvolysis with the aim of developing a rapid method to study polymer degradation 143 . The technique was applied to the study of various homopolymers and copolymers of different molecular weights under different chemical conditions, demonstrating reactive‐DESI could be used to study the degradation of polymers and assess their susceptibility to erosion.…”

“…applied reactive‐DESI to perform online monitoring of chain solvolysis with the aim of developing a rapid method to study polymer degradation. 143 The technique was applied to the study of various homopolymers and copolymers of different molecular weights under different chemical conditions, demonstrating reactive‐DESI could be used to study the degradation of polymers and assess their susceptibility to erosion. In recent months, alternative ambient ionization techniques have been evaluated for the purpose of reaction monitoring including ambient corona discharge ionization to study the N ‐alkylation of amines in ionic wind 144 and PSI to study on‐surface oxidation reactions.…”

Covalent Attachment and Detachment by Reactive DESI of Sequence‐Coded Polymer Taggants

“…[26] Performing DESI in a reactive mode consists of adding reagents in the sprayed solution to induce specific ion/molecule reaction at the surface. [27][28][29] Even though reactive DESI has been barely applied to synthetic polymers to date, [30] this technique could potentially be used for detaching covalently-bound taggants and decoding them by MS/MS sequencing. This concept was applied herein to hydrogels, which is a very important class of applied materials, [31][32] but also probably the trickiest to label with sequence-coded polymers.…”