Sheath liquid effects in capillary high-performance liquid chromatography–electrospray mass spectrometry of oligonucleotides

Fused-silica capillary columns of 200 μm inner diameter were packed with micropellicular, octadecylated, 2.3 μm poly(styrene–divinylbenzene) particles and applied to the separation of oligonucleotides by ion-pair reversed-phase high-performance liquid chromatography. Oligonucleotides were eluted at 50°C with gradients of 3–13% acetonitrile in 50 m M triethylammonium bicarbonate. Addition of sheath liquid to the column effluent allowed the detection of oligonucleotides by electrospray ionization mass spectrometry using full-scan data acquisition with a detectability comparable to that obtained with UV detection. The signal-to-noise ratios with different sheath liquids increased in the order isopropanol