Abstract

The separation of basic compounds in high-pH mobile phases results in extended retention, excellent peak shapes and good chromatographic efficiency. A severe decrease in sensitivity with electrospray mass spectrometric detection in positive ion mode (ESI +-MS) is expected under conditions that suppress analyte ionization in solution. We compared the responses of a large number of various basic drugs covering a wide range of hydrophobic (log P 0.09 to 7.6) and basic character (p K a 6.8–10) in LC–ESI +-MS/MS in 0.1% formic acid in water and acetonitrile, to responses in 10 mM ammonium hydrogencarbonate buffers of different pH (7.8–11), and acetonitrile. Contrary to common expectations, high-pH mobile phases do not affect negatively the responses of basic compounds in ESI +. Analyte responses and limits of detection are comparable, or most often better in high pH compared to acidic mobile phases.

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