Mixed-mechanism ionization to enhance sensitivity in atmospheric pressure ionization LC/MS

A novel dual-mechanism ionization technique for LC/MS/MS has been observed, characterized and applied to the quantitation of a tertiary amine-containi ng drug compound in dog plasma. This mixed-mechanism ionization approach ca n improve the sensitivity of the pneumatically assisted electrospray experi ment. Under conditions of higher than normal chromatographic how and lower electrospray voltage, approximately a 4-fold increase in sensitivity was re alized. A detection limit of 16 pg (45 fmol) on-column, and inter-day impre cision and inaccuracy of < 11 and < 15%, respectively, were obtained. A tra de-off in concentration sensitivity in favor of ease of sample preparation was made to increase sample throughput. Although results strongly suggest t hat mixed-mechanism ionization is in operation, and that pneumatically assi sted electrospray is a partial contributor to the overall ionization proces s, the exact nature of the second mechanism of ionization is unclear at thi s time. (C) 2000 Elsevier Science B.V. All rights reserved.