The analysis of basic drugs by LC/MS/MS with high pH mobile phases

ANYL 293

Tivadar Farkas and Liming Peng. Phenomenex, Inc, 411 Madrid Ave., Torrance, CA 90501
Chromatographic separations of basic compounds in high pH mobile phases show extended retention, excellent peak shapes and good efficiency. One possible drawback could be a severe decrease in sensitivity with electrospray MS detection under conditions that suppress analyte ionization in solution. In this study we evaluated the responses of a large number of basic drugs covering a wide range of polarity (log P 0.4-7.6) and pKa values (6.5-10) in ESI+ LC/MS/MS, in gradient elution mode, using mobile phases of either 0.1% formic acid or 10mM ammonium bicarbonate buffers at different pH (7.8-11) with acetonitrile. Contrary to common expectations, high pH mobile phases do not suppress basic compound ionization in ES; positive ions are formed abundantly and analyte responses, LODs and LOQs are comparable, or most often better in high pH compared to acidic mobile phases. We report the successful quantitation of 22 drugs with good linearity, precision and accuracy.