Development of reversed-phase chiral HPLC methods using mass spectrometry compatible mobile phases

The majority of chiral HPLC separations are performed in the normal-phase m ode using alcohol-modified hexane mobile phases. Normal-phase chiral HPLC m ethods are not routinely coupled with electrospray ionization mass spectrom etry (ESI-MS) because of the mobile phase incompatibility. In this study, w e investigated the use of ESI-MS compatible mobile phases for chiral HPLC m ethods. This would enable the sensitivity and selectivity of LC/MS to be ap plied to chiral HPLC analyses. We used a commercially available reversed-phase chiral HPLC column (Chiralc el(R) OD-R) that permits the use of aqueous organic-modified mobile phases. This paper describes the development of direct, isocratic, and simple reve rsed-phase chiral HPLC methods for the separation of enantiomers of benzoin , indapamide, 2-phenylbutyric acid, 3-phenylbutyric acid, trans-2-phenylcyc lopropane-1- carboxylic acid, verapamil hydrochloride, and pindolol. In addition, we also demonstrate that the reversed-phase chiral HPLC method s developed in this study can be directly coupled with ESI-MS without any m odifications. Examples of reversed-phase chiral high performance liquid chr omatography-mass spectrometry (RP Chiral-LC/MS) methods are shown for indap amide and pindolol.