title: HPLC method for determination of in vitro delivery through and into porcine skin of adefovir (PMEA).
abstract: A simple HPLC/UV method for the determination of the transdermal permeation and dermal penetration of a broad-spectrum antiviral drug adefovir (PMEA) was developed. The separation was achieved on a C18 column with the mobile phase composed of 10 mM KH2PO4 and 2 mM Bu4NHSO4 at pH 6.0 and 7% acetonitrile. The method was validated with respect to selectivity, linearity (0.1-50 microg/ml), precision, accuracy, and stability. Transdermal permeation of 2% PMEA was studied in vitro using the Franz diffusion cell and porcine skin. The flux values were 1.8, 3.0, and 0.6 microg/cm2/h from aqueous donor samples at pH 3.4 and 7.4, and isopropyl myristate, respectively. The respective skin concentrations at 48 h were 294, 263, and 971 microg/g from these vehicles. These results will serve as a lead for further studies on transdermal and topical delivery of antivirals from the group of acyclic nucleoside phosphonates.
authors.affiliation: Centre for New Antivirals and Antineoplastics, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, 50005 Hradec Králové, Czech Republic. katerina.vavrova@faf.cuni.cz
authors.forename: Katerina
authors.initials: K
authors.lastname: Vávrová
authors.forename: Katerina
authors.initials: K
authors.lastname: Lorencová
authors.forename: Jana
authors.initials: J
authors.lastname: Klimentová
authors.forename: Jakub
authors.initials: J
authors.lastname: Novotný
authors.forename: Alexandr
authors.initials: A
authors.lastname: Hrabálek
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D000279:Administration, Cutaneous; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D066298:In Vitro Techniques; D063065:Organophosphonates / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013552:Swine
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; C053001:adefovir; D000225:Adenine