Matrix-Assisted Ionization-Ion Mobility Spectrometry-Mass Spectrometry: Selective Analysis of a Europium–PEG Complex in a Crude Mixture

Abstract

Abstract. The analytical utility of a new and simple to use ionization method, matrixassisted ionization (MAI), coupled with ion mobility spectrometry (IMS) and mass spectrometry (MS) is used to characterize a 2-armed europium(III)-containing poly(-ethylene glycol) (Eu-PEG) complex directly from a crude sample. MAI was used with the matrix 1,2-dicyanobenzene, which affords low chemical background relative to matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI). MAI provides high ion abundance of desired products in comparison to ESI and MALDI. Inductively coupled plasma-MS measurements were used to estimate a maximum of 10% of the crude sample by mass was the 2-arm Eu-PEG complex, supporting evidence of selective ionization of Eu-PEG complexes using the new MAI matrix, 1,2-dicyanobenzene. Multiply charged ions formed in MAI enhance the IMS gas-phase separation, especially relative to the singly charged ions observed with MALDI. Individual components are cleanly separated and readily identified, allowing characterization of the 2-arm Eu-PEG conjugate from a mixture of the 1-arm Eu-PEG complex and unreacted starting materials. Size-exclusion chromatography, liquid chromatography at critical conditions, MALDI-MS, ESI-MS, and ESI-IMS-MS had difficulties with this analysis, or failed.

Novel ionization processes for use in mass spectrometry: ‘Squeezing’ nonvolatile analyte ions from crystals and droplets

“…Using an i MAI‐IMS‐MS approach, structural information was obtained by cross‐section analyses of the folding transitions of lysozyme, a protein associated with neurodegenerative diseases . We demonstrated analytical examples where conventional MALDI was difficult or failed, while MAI produced the desired results providing a molecular view of, e.g., endogenous and exogenous chemical compositions . Importantly, irrespective of the new methods employed to engage with the new ionization processes, ESI‐like charge states are observed.…”

“…Multiply charged protein ions are readily sequenced by an ETD approach providing a means of gas‐phase peptide/protein sequencing directly from surfaces . Liquid chromatography (LC) can be hyphenated with solvent‐based inlet ionization, as is the case with ESI, and fractionation is an obvious choice with vacuum ionization, as is the case with MALDI. Interfacing with IMS adds a useful separation of gas‐phase ions from mixtures and, when combined with LC approaches, permits powerful deconvolution of sample complexity, sometimes even of isomers .…”

“…Therefore, the charging and desolvation are associated with the matrix:analyte traversing through the cold or hot inlet tube, reducing the ion source to a feature intrinsically available with any atmospheric pressure ionization mass spectrometer without having to apply additional energy. A variety of different commercial MALDI and ESI sources have been employed for LSI and imaging applications including those from Thermo, Waters, and Bruker mass spectrometers . Recently, a miniature portable mass spectrometer was fitted with an LSI source …”

“…Quantitative information has been extracted from tissue and directly from high salt content solutions such as urine from a new‐born using this simple approach . A direct comparison of a potential magnetic resonance imaging (MRI) agent exemplified the efficiency of the MAI‐IMS‐MS approach over those of ESI‐ and MALDI‐IMS‐MS in terms of sensitivity and benefits from the additional IMS separation (peak capacity) achieved through the new ionization proceses . Carbohydrate conjugates have been ionized with these technologies for the first time where traditional methods failed .…”

Mass Spectrometry Imaging: A Review of Emerging Advancements and Future Insights

“…84 For separation of analytes, ion mobility has been a popular choice, as it can and has been seamlessly integrated into MALDI-MSI workflows, such as demonstrated by Trimpin and co-workers. 85 Enhancements to the sensitivity were recently made by the McLean group using a silver-sputtered matrix coating. 86 Ion mobility has also been recently demonstrated to be highly effective for coupling with ambient ionization techniques, such as LAESI, LESA, and DESI.…”