The effect of beta-cyclodextrin on liquid chromatography/electrospray-mass spectrometry analysis of hydrophobic drug molecules.
Cyclodextrins (CDs) are widely used in the pharmaceutical industry for their capability of improving bioavailability, solubility, or stability of drugs via the formation of soluble inclusion complexes. CDs have also been widely used in various chemical analysis methods. In this work, liquid chromatography/electrospray mass spectrometry (LC/ESI-MS) analysis for four different drugs (imipramine, desipramine, propranolol, and naproxen) that form inclusion complexes with CDs was performed in the presence and absence of beta-CD. These drugs are subject to nonspecific adsorption when brought into contact with plastics, such as HPLC tubing, sample collection and preparation apparatus, etc. Inclusion of the CD in the samples reduces this nonspecific adsorption due to competitive complex formation between the CD and the analyte. ESI-MS ion intensities increased when beta-CD was included in the sample with concentrations up to 1% (w:v), with a diverter valve installed post LC column. The degree of increased ion signal correlated with the beta-cyclodextrin:analyte binding constant. beta-CD appeared to elute within the void volume time and was observed in a full spectrum scan among the different analyte samples with up to 0.01% beta-CD injected directly to the LC/MS system with the diverter valve switched inline with the mass spectrometer. The use of the diverter valve allowed for direct injection of samples containing up to 1% beta-CD to the LC/MS without any deterioration of analyte ion signal.
Sun
Li
L
WP75A-303, Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA. li_sun@merck.com
Stenken
Julie A
JA
D000929:Antidepressive Agents, Tricyclic / Q000032:analysis; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003891:Desipramine / Q000032:analysis; D007099:Imipramine / Q000032:analysis; D012015:Reference Standards; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000929:Antidepressive Agents, Tricyclic; D047392:beta-Cyclodextrins; C031215:betadex; D007099:Imipramine; D003891:Desipramine