Combining ion pairing agents for enhanced analysis of oligonucleotide therapeutics by reversed phase-ion pairing ultra performance liquid chromatography (UPLC).

The burgeoning field of oligonucleotide therapeutics is based upon synthetically derived biopolymers comprised of relatively simple RNA and DNA building blocks. Significant gains in knowledge around mechanisms of action (RNA interference, RNA splicing, etc.) and oligonucleotide design (ASO, siRNA, DsiRNA, miRNA, locked nucleic acid, etc.

Chemistry at the 2' position of constituent nucleotides controls degradation pathways of highly modified oligonucleotide molecules.

A forced degradation study of a proprietary short interfering RNA (siRNA) molecule most of whose constituent nucleotides have been modified at the 2' position was conducted to assess degradation pathways and stability liabilities. The siRNA was subjected to various conditions as a solid and in solution followed by analysis with reverse-phase ultra-performance liquid chromatography-mass spectrometry. Positional isomers of degradants gave rise to multiple chromatographic peaks with identical masses.

Using a nanoelectrospray-differential mobility spectrometer-mass spectrometer system for the analysis of oligosaccharides with solvent selected control over ESI aggregate ion formation.

Differential mobility spectrometry (DMS), also commonly referred to as high field asymmetric waveform ion mobility spectrometry (FAIMS) is a rapidly advancing technology for gas-phase ion separation. The interfacing of DMS with mass spectrometry (MS) offers potential advantages over the use of mass spectrometry alone. Such advantages include improvements to mass spectral signal/noise, orthogonal/complementary ion separation to mass spectrometry, enhanced ion and complexation structural analysis, and the potential for rapid analyte quantitation.

Rapid separation and quantitative analysis of peptides using a new nanoelectrospray- differential mobility spectrometer-mass spectrometer system.

Differential mobility spectrometry (DMS) (see Buryakov, I. A.; Krylov, E.

Characterization of gas-phase molecular interactions on differential mobility ion behavior utilizing an electrospray ionization-differential mobility-mass spectrometer system.

Differential mobility spectrometry (DMS) is a rapidly advancing technology for gas-phase ion separation. The interfacing of DMS with mass spectrometry (MS) offers potential advantages over the use of mass spectrometry alone. Such advantages include improvements to mass spectral signal/noise ratios, orthogonal/complementary ion separation to mass spectrometry, enhanced ion and complexation structural analysis, and potential for rapid analyte quantitation.