Journal of Chromatography A, 869 (2000) 159–170 www.elsevier.com / locate / chroma Optimized stationary phases for the high-performance liquid chromatography–electrospray ionization mass spectrometric analysis of basic pharmaceuticals a, b c c * S.R. Needham , P.R. Brown , K. Duff , D. Bell a Pfizer, Inc., Candidate Synthesis Enhancement and Evaluation Group, Eastern Point Road, Groton, CT 06340, USA b Chemistry Department, University of Rhode Island, Kingston, RI 02881, USA c Restek Corporation, Bellefonte, PA 16823, USA Abstract Stationary phases were investigated for HPLC coupled with electrospray ionization mass spectrometry (ESI-MS) for the analysis of basic drugs. Tricyclic antidepressants (TCAs) and b-blockers were used as model solutes. The functional groups, pentafluorophenyl (PFP), OH, CN or CH were attached to the silica via a propyl chain. The effects of these stationary 3 phases as well as C and C phases on retention and peak shape of the basic drugs were studied. The CN and PFP phases 8 18 adequately retained (t of 2 to 6 min) the basic drugs when the mobile phase was composed of 90% acetonitrile, whereas R with the C , C and C phases, less than 40% acetonitrile had to be used to provide adequate retention of the basic drugs. 4 8 18 Because acetonitrile provides better desolvation in ESI than an aqueous solvent, it produces an increased MS signal. As an example of the HPLC–ESI-MS analysis of the b-blocker, pindolol, on a CN phase, the use of 90% acetonitrile in the mobile phase increased the ESI-MS signal by 790% when compared to a C phase which could use only 5% acetonitrile in the 18 mobile phase for retention of the solute. In addition, the CN and PFP phases provided better peak shape than the OH phase and the hydrophobic phases (C , C and C ) and ion-pairing or ion-suppressing agents were not required. The retention 4 8 18 behavior of the TCAs and b-blockers on each of the phases is described.  2000 Elsevier Science B.V. All rights reserved. Keywords: Stationary phases, LC; Antidepressants, tricyclic; Beta-blockers 1. Introduction velopment and improvement of the interface between the HPLC and the MS systems [4,5]. A second focus For the past decade, high-performance liquid has been to improve ion transmission in the mass chromatography–mass spectrometry (HPLC–MS) spectrometer for improved sensitivity and resolution has taken its rightful place as a routine technique in [6,7]. Other research has focused on the effects of analytical laboratories, especially in the pharmaceu- the HPLC mobile phase conditions on electrospray tical and biotechnology industries [1–3]. Initially ionization (ESI) MS signals [8,9]. There is, however, instrumental researchers focused mainly on the de- still a need for improving detection limits in the HPLC–MS analysis of pharmaceutical compounds in various matrices. We therefore investigated novel *Corresponding author. Tel.: 11-860-4418-550; fax: 11-860- stationary phases in order to improve detection limits 7157-547. in HPLC–MS and provide good peak shape with the E-mail address: shane r needham@groton.pfizer.com (S.R. ]] Needham) use of optimal ESI-MS solvents. These new station- 0021-9673 / 00 / $ – see front matter  2000 Elsevier Science B.V. All rights reserved. PII: S0021-9673(99)00986-3