Electrospray photoionization (ESPI) liquid chromatography/mass spectrometry for the simultaneous analysis of cyclodextrin and pharmaceuticals and their binding interactions

• Published in: Rapid communications in mass spectrometry 2008-01, Vol.22 (4), p.541-548
• Main Authors: Short, Luke C., Syage, Jack A.
• Format: Article
• Language: English
• Subjects: Chromatography, High Pressure Liquid - methods; Cyclodextrins - analysis; Cyclodextrins - chemistry; Drug Carriers - analysis; Drug Carriers - chemistry; Kinetics; Pharmaceutical Preparations - analysis; Pharmaceutical Preparations - chemistry; Photochemistry - methods; Reproducibility of Results; Sensitivity and Specificity; Spectrometry, Mass, Electrospray Ionization - methods
• ISSN: 0951-4198; 1097-0231
• DOI: 10.1002/rcm.3396

We report on the use of a multimode electrospray ionization/atmospheric pressure photoionization source (ESI/APPI or ESPI for short) with liquid chromatography/mass spectrometry (LC/MS) to measure all components of a mixed‐polarity liquid sample containing: (1) low‐polarity component (hormone, pharmaceutical or sterol), (2) polar component (cyclodextrin substrate), and (3) bound polar complex. The ESPI source has several advantages over both single ESI and multimode electrospray ionization/chemical ionization (ESCI) analysis, including an enhanced bound‐complex detection and better performance at lower solvent flow rates. Relative binding constants are determined with (i) ESI mode, resulting in relative R(ESI‐MS) values, and (ii) both ESI and APPI modes, providing relative KD values. We find that low molecular‐substitution (Ms) values of cyclodextrin, i.e., Ms = 0.4, preferentially bind to the low‐polarity compounds tested. This investigation is intended to demonstrate the feasibility of ESPI as an additional tool for investigating mixed‐polarity binding systems, providing mass‐specific data for all solution components, both polar and non‐polar. Copyright © 2008 John Wiley & Sons, Ltd.