title: A direct sensitized fluorimetric determination of 5,10,15,20-tetra(m-hydroxyphenyl)chlorin [m-THPC (Foscan)] in human plasma using a cyclodextrin inclusion complex.
abstract: The 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (m-THPC) (Foscan) is a photosensitizer used in the photodynamic therapy (PDT) of cancers which is currently under clinical trial. The formation of a m-THPC inclusion complex with dimethyl-beta-cyclodextrin (Me-beta-CD) in solution was demonstrated on the basis of circular dichroism experiments. A 1:2 complex stoichiometry was found and an inclusion constant beta 2 = 2.8(+/- 0.4) x 10(10) M-2 was determined. The formation of such a complex was shown to enhance the m-THPC fluorescence intensity. It could be exploited to improve the sensitivity of the direct m-THPC detection in human plasma. Optimization of the operating conditions shows that the best results were obtained by the addition of 100 microL of a concentrated Me-beta-CD solution (3.2 x 10(-2) M) to 1 mL plasma samples. Compared to the standard conditions, a 90% increase in sensitivity was obtained. The proposed analytical method which showed a linear response function [0-300 ng mL-1 (440 pM)] and a low limit of detection [1.5 ng mL-1 (2 pM) (S/N = 3)] appears, especially due to the absence of metabolism, a simple and specific method suitable for pharmacokinetics studies in patients.
authors.affiliation: Laboratoire de Chimie Analytique, Faculté de Pharmacie Paris XI, 5 rue J.-B. Clément, F-92296 Chatenay-Malabry, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Desroches
authors.forename: A
authors.initials: A
authors.lastname: Kasselouri
authors.forename: O
authors.initials: O
authors.lastname: Bourdon
authors.forename: P
authors.initials: P
authors.lastname: Chaminade
authors.forename: J
authors.initials: J
authors.lastname: Blais
authors.forename: P
authors.initials: P
authors.lastname: Prognon
mesh_terms: D006801:Humans; D008652:Mesoporphyrins / Q000097:blood*; D017319:Photosensitizing Agents / Q000097:blood*; D013053:Spectrophotometry
chemical_list: D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin