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ANALYST, 1999, VOL. 124, PP. 391-396
Rapid Automated Spectrophotometric Competitive Complexation Studies of Drugs with Cyclodextrins Using the Flow Injection Gradient Ôechnique: Tricyclic Antidepressant Drugs with a-cyclodextrin
Maria E. Georgioua, Constantinos A. Georgioub and Michael A. Koupparis*,a
aLaboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis, Kouponia, 157 71 Athens, Greece
bChemistry Laboratory, Agricultural University of Athens, 75 Iera Odos, 118 55 Athens, Greece
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An automated gradient flow injection (FI) spectrophotometric technique for competitive complexation studies of tricyclic antidepressant drugs with a-cyclodextrin (a-CD) using Methyl Orange (MO) as a probe is described. Formation constants for the complexes were determined utilising the total information contained in transient FI signals at 510 nm, the ëmax of the MO probe. The study was carried out rapidly in three steps: (a) calibration of the FI concentration gradient by injection of p-nitrophenol in a buffered carrier stream, (b) determination of the probe-a-CD complex formation constant by injecting á-CD into the probe carrier stream and (c) determination of the drug-a-CD complex formation constant by injecting a-CD into the probe-drug carrier stream. In this way the preparation and measurement of a great number of mixed drug-probe-a-CD solutions was automated, resulting in the fast and precise determination of complexation constants of ligands (drugs), that are optically transparent, with a-CD. Methyl Orange was found to be an excellent probe for a-CD in acidic solutions (pH 1.0) with a complexation constant of (5.3 ± 0.1) x 102 Ì-1. Complex formation constants determined at 26.5 ± 0.5 °C and pH 1.0 (HCl) utilising transient a-CD concentrations in the range (1-1000) x 10-4 Ì, were (1.2 ± 0.1) x 102 Ì-1 for protriptyline, (0.7 ± 0.1) x 102 Ì-1 for nortriptyline, (2.4 ± 0.1) x 102 Ì-1 for maprotiline, (1.4 ± 0.1) x 102 Ì-1 for doxepin, (1.13 ± 0.07) x 102 Ì-1 for amitriptyline and (1.3 ± 0.2) x 102 Ì-1 for imipramine. A 1:1 stoichiometry was found in all cases. The within- and between-run precisions ranged from 1.2 to 6.4% and from 4.2 to 15.4% (RSD), respectively. The determined complex formation constants were in good agreement with those in the literature. Using the proposed FI gradient technique, the tedious manual preparation of a great number of mixed solutions with variable a-CD to drug ratios and the subsequent spectrophotometric measurements are replaced by a single FI measurement lasting 80 s.
*Corresponding author.
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