Determination of the partition coefficient of triflupromazine between phosphatidylcholine vesicles and water by 19F nuclear magnetic resonance spin-lattice relaxation time measurement

Abstract

The 19F nuclear magnetic resonance (NMR) spin-lattice relaxation time ( T 1) of the trifluoromethyl signal of triflupromazine (TFZ) was measured in aqueous suspensions of phosphatidylcholine (lecithin) small unilamellar vesicles (SUV). The observed T 1 value depended on the concentration of SUV. Based on a simple two-site rapid exchange model, the partition coefficient ( K p) of TFZ between lecithin SUV and water was calculated from the relationship between the T 1 value and the lecithin concentration by using a nonlinear least-squares method. The obtained K p value (2.1±0.2×10 5) agreed well with that measured by a second-derivative spectrophotometric method. The 19F NMR T 1 method will be useful for the determination of partition coefficients of drugs having fluorine atom(s), especially for the drugs which do not have absorption in the ultraviolet or visible region, or for those having absorption but do not show any changes according to their incorporation into the lecithin bilayers. The method does not require any separation procedure that may disturb the equilibrium conditions.