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Review
. 2023 May 18;15(10):2356.
doi: 10.3390/polym15102356.

Matrix-Assisted Laser Desorption and Electrospray Ionization Tandem Mass Spectrometry of Microbial and Synthetic Biodegradable Polymers

Paola Rizzarelli  1 , Marco Rapisarda  1
Affiliations
Review

Matrix-Assisted Laser Desorption and Electrospray Ionization Tandem Mass Spectrometry of Microbial and Synthetic Biodegradable Polymers

Paola Rizzarelli et al. Polymers (Basel). .

Abstract

The in-depth structural and compositional investigation of biodegradable polymeric materials, neat or partly degraded, is crucial for their successful applications. Obviously, an exhaustive structural analysis of all synthetic macromolecules is essential in polymer chemistry to confirm the accomplishment of a preparation procedure, identify degradation products originating from side reactions, and monitor chemical-physical properties. Advanced mass spectrometry (MS) techniques have been increasingly applied in biodegradable polymer studies with a relevant role in their further development, valuation, and extension of application fields. However, single-stage MS is not always sufficient to identify unambiguously the polymer structure. Thus, tandem mass spectrometry (MS/MS) has more recently been employed for detailed structure characterization and in degradation and drug release monitoring of polymeric samples, among which are biodegradable polymers. This review aims to run through the investigations carried out by the soft ionization technique matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and electrospray ionization mass spectrometry (ESI-MS) MS/MS in biodegradable polymers and present the resulting information.

Keywords: ESI; MALDI; biodegradable polymers; characterization; degradation; drug delivery systems; multi stage mass spectrometry; tandem mass spectrometry.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of the most representative microbial and synthetic biodegradable polymers analyzed by MALDI and ESI-MS and MS/MS.
Figure 2
Figure 2
Bond cleavages leading to the diagnostic product ions from (a) ester/ester, (b) amide/amide, and (c) ester/amide sequences. (d) Enlarged portion of MALDI-TOF/TOF-MS/MS spectrum of the sodiated cyclic oligomers at m/z 1228.8 of the PEA-Pro sample (collision gas = argon) (reprinted from [54]).
Figure 3
Figure 3
Bond cleavages leading to the diagnostic product ions from (a) ester/ester, (b) amide/amide, and (c) ester/amide sequences. (d) Enlarged portion of MALDI-TOF/TOF-MS/MS spectrum of the sodiated dicarboxyl-terminated oligomers at m/z 1303.9 of the PEA-Pro sample (collision gas = argon) (reprinted from [54]).
Scheme 1
Scheme 1
Workflow Summarizing the MS-Based Analytical Strategy Developed for Full Characterization of PLGA Copolymers (reprinted from [84] with kind permission of ACS).
Figure 4
Figure 4
Laser DIUTHAME−spiralTOF mass spectra of (a) sample #2 (PLGA 75/25), (b) sample #3 (PLGA 65/35), and (c) sample #4 (PLGA 50/50), showing in-source fragments of the form C3H3O(C3H4O2)x(C2H2O2)y+, with x and y the number of intact LA and GA units, respectively. (d) LA molar content (%) calculated from product ion abundances measured for unfractionated samples (dotted lines in red for sample #2, green for sample #3, and blue for sample #4) and for nine fractions (colored squares) collected throughout the SEC profile of the three PLGA copolymer samples displayed in the background (reprinted from [84] with kind permission of ACS).
Figure 5
Figure 5
(a) CAD and (b) ETD MS2 spectra of the [M+2Na]2+ ion from the poly(lactide) 16-mer (m/z 637). The notation ln indicates linear fragments with n repeat units; the superscript gives the end groups (see text). (a) All CAD fragments are singly charged except for those marked by ‡, which carry 2+ charges (m/z 556.2, 565.2, 572.2, 592.2 and 601.2). (b) All ETD fragments are singly charged; ln* denotes doubly sodiated monocations, whereas the notations ln● and ln″ for vinyl-terminated fragments indicate the presence of 1 or 2 additional H atoms, respectively (both are present) (reprinted from [51] with kind permission of Wiley).
Scheme 2
Scheme 2
CAD pathways of sodiated poly(lactide) proceeding via (a) charge-remote 1,5-H rearrangement at the ester groups and (b) charge-induced 1,4-proton transfer at the hydroxy-terminated repeat unit; R = CH2CH2OCH3. The former reaction yields fragments with acid/hydroxy (lnAH) and ester/vinyl (lnRV) end groups and the latter truncated chains with the same end groups as the precursor ion (ester/hydroxy, lnHR) (reprinted from [51] with kind permission of Wiley).
Figure 6
Figure 6
ESI-MS/MS spectrum of the sodium adducts of poly (δ-valerolactone–6-ε-methylcaprolactone) macromolecules and containing one mCL comonomer unit at m/z 1113. “A” symbolizes the structure of the precursor ion bearing ethylene glycol as an end group (R = H) (adapted from [55]).
Scheme 3
Scheme 3
Possible fragmentation pathways for sodium adducts of poly (δ-valerolactone–6-methyl-ε-caprolactone) macromolecules at m/z 1113; R1 = P(dVL-co-mCL) or H, R2 = H in dVL unit, R3 = CH3 in mCL unit (reprinted from [55]).
Figure 7
Figure 7
Tandem MS analysis by ETD. (a) Schematic of all the possible fragment ions with cross-ring cleavages for a head-to-tail (HT) subunit orientation. M-60 and M-192 are the diagnostic fragment ions for HT orientation. (b) Schematic of all the possible fragment ions with cross-ring cleavages for a tail-to-head (TH) subunit orientation. M-74, M-118, M-162 and M-178 are the diagnostic fragment ions for TH orientation. (c) ETD MS/MS spectrum of tri-sodiated 15 mer ([AB15 + 3Na]3+, m/z 1305). Note, at each subunit dissociation diagnostic fragment ions of both subunit orientations are present (reprinted from [86] with kind permission of ACS).
Figure 8
Figure 8
The ESI-MS/MS spectrum (positive-ion mode) of the PHA oligomers’ parent ion at m/z 1027 (reprinted from [125]).
Figure 9
Figure 9
MS/MS spectra of [M6 + S + Na]+ m/z 487 (S = MeOH) (a) and m/z 491 (S = CD3OD) (b) following solvolysis of uniform CPLA (n = 6) (reprinted from [114] with kind permission of Wiley).
Scheme 4
Scheme 4
Chemical structures of linear (LPLA) and cyclic polylactic acid (CPLA), and definitions of ion series A, B, C, and C′ in the MS/MS spectra (reprinted from [114] with kind permission of Wiley).
Figure 10
Figure 10
Product ions and structures of (A) lanosterol and (B) IS (reprinted from [110] with kind permission of Elsevier).
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