Capillary isotachophoresis-nanoelectrospray ionization-selected reaction monitoring MS via a novel sheathless interface for high sensitivity sample quantification.

A novel sheathless capillary isotachophoresis (CITP/CZE)-mass spectrometry (MS) interface featuring a large inner diameter (i.d.) separation capillary, and a detachable small i.d. porous electrospray ionization (ESI) emitter was developed in this study to simultaneously achieve large sample loading capacity and stable nanoESI operation. Crucial operating parameters, including sample loading volume, flow rate, and separation window, were systematically investigated to attain optimum CITP/CZE separation efficiency and MS detection sensitivity. The performance of CITP/CZE-nanoESI-MS using the new sheathless interface was evaluated for its achievable low limit of quantification (LOQ) by analyzing targeted peptides, leu-enkephalin and angiotensin II, spiked in a BSA tryptic digest matrix at different concentrations. A linear dynamic range spanning 4.5 orders of magnitude and a 10 pM LOQ with measurement reproducibility of the CV < 22% were obtained experimentally for both targeted peptides, representing a 5-fold sensitivity improvement as compared to using the sheath liquid interface developed previously.1.