Photodegradation study of a new activator of the cystic fibrosis chloride channel, the 6-hydroxy-10-chlorobenzo[c]quinolizinium chloride (MPB-07).
The photodegradation of 6-hydroxy-10-chlorobenzo[c]quinolizinium chloride (MPB-07), a new activator of the transmembrane conductance regulator chloride channel, was studied in aqueous solutions exposed to artificial daylight (2300 Lux intensity). Various conditions of pH, concentration, and temperature were used. MPB-07 concentration was determined at regular time intervals by reversed-phase HPLC. MPB-07 stability was also studied at pH 7.4 in the dark. Results showed that in all the conditions tested MPB-07 underwent rapid photodegradation, apparently following first-order kinetics. Rate constants were dependent on the initial MPB-07 concentration, temperature, and pH. At pH 7.4, and for concentrations from 1 to 125 microM, half-lives ranged from 0.681 +/- 0.047 to 4.54 +/- 0.28 h. The Arrhenius plot was linear and activation energy was calculated to be 20.7 kJ x mol(-1). Analysis by chemical ionization-mass spectrometry showed that the chlorine atom of the MPB-07 molecule might be replaced by an OH group during the photodegradation process. In the dark, MPB-07 in solutions at pH 7.4 was found to be stable over a 6-week period. In conclusion, MPB-07 is a highly photolabile molecule that should be carefully protected from light when used.
Olivier
Jean-Christophe
JC
Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté de Médecine et Pharmacie 34, rue du Jardin des Plantes, B.P. 199, 86005 Poitiers Cedex, France.
Manceau
Joachim
J
Marivingt-Mounir
Cécile
C
Mettey
Yvette
Y
Vierfond
Jean-Michel
JM
Couet
William
W
D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D008027:Light; D011807:Quinolizines / Q000032:analysis / Q000737:chemistry*; D013696:Temperature
C451901:6-hydroxy-10-chlorobenzo(c)quinolizinium; D011807:Quinolizines; D019005:Cystic Fibrosis Transmembrane Conductance Regulator