title: 19F NMR spectrometric determination of the partition coefficients of some fluorinated psychotropic drugs between phosphatidylcholine bilayer vesicles and water.
abstract: A simple 19F NMR spectrometric method was proposed for the determination of the partition coefficients of fluorinated psychotropic drugs, trifluoperazine (TFPZ), flunitrazepam (FNZ) and flurazepam (FZ) between phosphatidylcholine (PC) bilayer of small unilamellar vesicles (SUVs) and water (buffer). Each 19F NMR spectrum of these drugs in the presence of PC SUV showed a single signal accompanying a PC concentration-depending shift change and broadening, which indicated a fast exchange of these drugs between the water phase and the PC bilayer of SUV. From the relationship between the 19F chemical shift change (Deltadelta) of each drug and the PC concentration, the molar partition coefficients (K(p)'s) were calculated and obtained with a good precision of RSD below 6%. The fractions of the partitioned drugs calculated by using the obtained K(p)-values were in a good agreement with the experimental values. The results demonstrate that the 19F NMR method can be usefully applied to the determination of partition coefficients of many drugs having fluorine atom(s) without any separation procedure, especially for drugs which do not have absorption in the ultraviolet or visible region, or those having absorption but show insignificant spectral changes according to their incorporation to PC bilayers (e.g. FNZ).
authors.affiliation: Kyoto Pharmaceutical University, 5 Nakauchicho, Misasagi, Yamashina-ku, 607-8414, Kyoto, Japan.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Omran
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kitamura
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Takegami
authors.forename: Manabu
authors.initials: M
authors.lastname: Kume
authors.forename: Megumi
authors.initials: M
authors.lastname: Yoshida
authors.forename: Abdel Aziz Y
authors.initials: AA
authors.lastname: El-Sayed
authors.forename: Mahmoud H
authors.initials: MH
authors.lastname: Mohamed
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdel-Mottaleb
mesh_terms: D005461:Fluorine / Q000032:analysis / Q000493:pharmacokinetics; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D010713:Phosphatidylcholines / Q000378:metabolism*; D011619:Psychotropic Drugs / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D014867:Water / Q000378:metabolism
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D011619:Psychotropic Drugs; D014867:Water; D005461:Fluorine