title: Electrospray photoionization (ESPI) liquid chromatography/mass spectrometry for the simultaneous analysis of cyclodextrin and pharmaceuticals and their binding interactions.
abstract: 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 K(D) 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.
authors.affiliation: Syagen Technology, Inc., 1411 Warner Ave., Tustin, CA 92780-6461, USA. lshort@syagen.com
authors.forename: Luke C
authors.initials: LC
authors.lastname: Short
authors.forename: Jack A
authors.initials: JA
authors.lastname: Syage
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003505:Cyclodextrins / Q000032:analysis* / Q000737:chemistry*; D004337:Drug Carriers / Q000032:analysis / Q000737:chemistry*; D007700:Kinetics; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry*; D010777:Photochemistry / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D003505:Cyclodextrins; D004337:Drug Carriers; D004364:Pharmaceutical Preparations