Magic matrices for ionization in mass spectrometry

Abstract. In matrix-assisted ionization (MAI), analyte incorporated in a small molecule matrix is introduced into an aperture linking atmospheric pressure with the vacuum of a mass spectrometer. Gas-phase analyte ions are spontaneously produced without use of a laser or high voltage. Here we investigate analyte and background ion abundances upon addition of ammonium salts to various MAI matrix/analyte solutions. Regardless of the ammonium salt or matrix used, chemical background ions are suppressed and/or analyte ion abundance improved for basic small molecules, peptides, and proteins. Background ion abundances increase with increasing inlet temperature, but are suppressed with addition of any of a variety of ammonium salts without much effect on the total ion abundances of the analyte ions. However, at lower inlet temperature using the matrices 2-bromo-2-nitropropane-1,3-diol, 1,2-dicyanobenzene, and 3-nitrobenzonitrile (3-NBN), analyte ion abundance increases and any chemical background decreases upon addition of ammonium salt. The improvement in sensitivity using 3-NBN with ammonium salt allows full acquisition mass spectra consuming as little as 1 fmol of ubiquitin. More complete peptide coverage for 100 fmol of a BSA tryptic digest, and increased sensitivity of drugs spiked in urine and saliva were observed after ammonium salt addition to the 3-NBN matrix.

“…However, improved ion abundance is obtained using the Orbitrap Exactive for shorter duration when heat is applied to the inlet [18]. Inlet temperature above ca.…”

Section: Ammonium Salt Addition With Peptide and Protein Analytesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Improving the Sensitivity of Matrix-Assisted Ionization (MAI) Mass Spectrometry Using Ammonium Salts

Chubatyi

McEwen

2015

“…These matrices produce abundant ions from incorporated analyte simply by exposure to the vacuum of a mass spectrometer at the atmospheric pressure inlet aperture. A number of analytically useful MAI matrices that spontaneously produce gas-phase analyte ions without use of a laser, a high voltage source, or any external energy source have been reported [20]. The first MAI matrix discovered that does not require a heated inlet, and still one of the most useful, is 3-nitrobenzonitrile (3-NBN) [18,19].…”

Section: Introductionmentioning

confidence: 99%

High Sensitivity Analysis of Nanoliter Volumes of Volatile and Nonvolatile Compounds using Matrix Assisted Ionization (MAI) Mass Spectrometry

Hoang

Pophristić

Horan

et al. 2016

Abstract. First results are reported using a simple, fast, and reproducible matrixassisted ionization (MAI) sample introduction method that provides substantial improvements relative to previously published MAI methods. The sensitivity of the new MAI methods, which requires no laser, high voltage, or nebulizing gas, is comparable to those reported for MALDI-TOF and n-ESI. High resolution full acquisition mass spectra having low chemical background are acquired from low nanoliters of solution using only a few femtomoles of analyte. The limit-of-detection for angiotensin II is less than 50 amol on an Orbitrap Exactive mass spectrometer. Analysis of peptides, including a bovine serum albumin digest, and drugs, including drugs in urine without a purification step, are reported using a 1 μL zero dead volume syringe in which only the analyte solution wetting the walls of the syringe needle is used in the analysis.

“…The charge separation process in MAI is hypothesized to be a sublimation-driven process through crystal fracturing of compounds that triboluminescence [1,2,10]. Some europiumcontaining compounds are known to triboluminesce [59][60][61][62][63], potentially contributing to the overrepresentation of the europium-containing product.…”

Section: Ionizationmentioning

confidence: 99%

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

Fischer

Lutomski

El‐Baba

et al. 2015

Self Cite

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.