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-containing drug compound in dog plasma. This mixed-mechanism ionization approach can improve the sensitivity of the pneumatically assisted electrospray experiment. Under conditions of higher than normal chromatographic flow and lower electrospray voltage, approximately a 4-fold increase in sensitivity was realized. A detection limit of 16 pg (45 fmol) on-column, and inter-day imprecision and inaccuracy of < 11 and < 15%, respectively, were obtained. A trade-off in concentration sensitivity in favor of ease of sample preparation was made to increase sample throughput. Although results strongly suggest that mixed-mechanism ionization is in operation, and that pneumatically assisted electrospray is a partial contributor to the overall ionization process, the exact nature of the second mechanism of ionization is unclear at this time.
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Department of Pharmacokinetics, Dynamics and Metabolism, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA.
Hoffman
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KL
Pace
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Rossi
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DT
D000818:Animals; D001274:Atmospheric Pressure; D001774:Blood Chemical Analysis; D002853:Chromatography, Liquid / Q000592:standards*; D004285:Dogs; D013058:Mass Spectrometry / Q000592:standards*; D004364:Pharmaceutical Preparations / Q000032:analysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D004364:Pharmaceutical Preparations