Vávrová Katerina, Lorencová Katerina, Klimentová Jana, Novotný Jakub, Hrabálek Alexandr
Centre for New Antivirals and Antineoplastics, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, 50005 Hradec Králové, Czech Republic.
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Jun 15;853(1-2):198-203. doi: 10.1016/j.jchromb.2007.03.012. Epub 2007 Mar 18.
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.
开发了一种简单的高效液相色谱/紫外法，用于测定广谱抗病毒药物阿德福韦（PMEA）的经皮渗透和皮肤渗透情况。在C18柱上进行分离，流动相由pH值为6.0的10 mM磷酸二氢钾和2 mM硫酸四丁铵以及7%乙腈组成。该方法在选择性、线性（0.1 - 50微克/毫升）、精密度、准确度和稳定性方面进行了验证。使用Franz扩散池和猪皮在体外研究了2% PMEA的经皮渗透情况。来自pH值为3.4和7.4的水性供体样品以及肉豆蔻酸异丙酯的通量值分别为1.8、3.0和0.6微克/平方厘米/小时。在48小时时，这些载体对应的皮肤浓度分别为294、263和971微克/克。这些结果将为进一步研究无环核苷膦酸类抗病毒药物的经皮和局部给药提供线索。
