High-throughput chiral liquid chromatography/tandem mass spectrometry

Chiral liquid chromatography is a well-established area of bioanalytical ch emistry and is often used during the processes of drug discovery and develo pment. The development and use of a chiral drug require the understanding o f the pharmacokinetic characteristics of each of the enantiomers, including potential differences in their absorption, distribution, metabolism, and e xcretion. Chromatographic techniques coupled to atmospheric pressure ioniza tion-tandem mass spectrometry have shown potential as sensitive and robust tools in the quantitative and qualitative determination of enantiomers in b iologic fluids and tissue extracts. However, development of a chiral liquid chromatography method requires time-consuming procedures that are devised empirically. Clearly, there is an incentive to design chromatographic appro aches that are easy to use, compatible with mass spectrometry ionization in terface conditions, exhibit relatively short run times without compromising sensitivity, and offer a broad analyte specificity, For these reasons, the present paper explores the feasibility of the bonded macrocyclic glycopept ide phases (teicoplanin and vancomycin) for analysis by chiral liquid chrom atography/tandem mass spectrometry. Ritalinic acid, pindolol, fluoxetine, o xazepam, propranolol, terbutaline, metoprolol, and nicardipine were tested in this study. Furthermore, an example of a simultaneous chiral LC/MS/MS de tection (chromatographic run time similar to 10 min) of four pharmaceutical products resulting in baseline resolutions of all four pairs of enantiomer s is presented. Methanol, an MS-compatible mobile phase, was utilized in al l the experiments. Copyright (C) 2000 John Wiley & Sons, Ltd.