The School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, New Zealand.
J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Apr 30;1170:122609. doi: 10.1016/j.jchromb.2021.122609. Epub 2021 Mar 1.
Dexamethasone is a fluorinated derivative of the natural glucocorticoid, cortisone, with a very high systemic anti-inflammatory effect. In this study, a simple and rapid high performance liquid chromatography (HPLC) method was developed and validated to quantify dexamethasone and its prodrug dexamethasone sodium phosphate in skin permeation studies. The separation of both the compounds was achieved on a Vydac Denali C column(250 × 4.6 mm, 5 μm) with a mobile phase composed of 5 mM ammonium acetate buffer-acetonitrile-methanol (43:32:25, v/v) at a flow rate of 0.9 mL/min and UV detection at 240 nm. The standard curves were found to be linear in the range from 0.5 to 100 µg/mL for both the drugs and the method could successfully separate the drug peaks from interfering peaks of endogenous skin constituents. Accuracy values of both the drugs were within 98.60 to 108.60% (intra-day) and 98.70 to 107.20% (inter-day) and precision values were within 2% at the studied concentrations. The developed method was used to investigate the effect of microneedles on transdermal delivery of dexamethasone sodium phosphate. The hydrolysis of dexamethasone sodium phosphate to dexamethasone in the presence of rat skin homogenate and rat plasma was also evaluated to confirm the conversion that occurs during skin permeation and in the blood circulation. The skin permeation and deposition characteristics of microneedle-assisted diffusion were compared to those achieved by passive diffusion. The observed data demonstrated that transdermal permeation of dexamethasone is significantly enhanced with microneedle pretreatment of rat skin, showing a marked increase in flux and permeability coefficient, compared to passive diffusion. This simple isocratic HPLC method can, be effectively applied for the evaluation of skin permeation of topical/transdermal dexamethasone formulations.
地塞米松是天然糖皮质激素可的松的氟化衍生物，具有很高的全身抗炎作用。在这项研究中，开发并验证了一种简单快速的高效液相色谱（HPLC）方法，用于定量皮肤渗透研究中的地塞米松及其前体地塞米松磷酸钠。两种化合物的分离是在 Vydac Denali C 柱（250×4.6mm，5μm）上实现的，流动相由 5mM 乙酸铵缓冲液-乙腈-甲醇（43:32:25，v/v）组成，流速为 0.9mL/min，UV 检测波长为 240nm。标准曲线在 0.5 至 100μg/mL 范围内对两种药物均呈线性，该方法能够成功地将药物峰与内源性皮肤成分的干扰峰分离。两种药物的准确度值在 98.60%至 108.60%（日内）和 98.70%至 107.20%（日间）之间，在研究浓度下精密度值均在 2%以内。所开发的方法用于研究微针对面磷酰胺透皮给药的影响。还评估了在大鼠皮肤匀浆和大鼠血浆存在下地塞米松磷酸钠转化为地塞米松的水解作用，以确认在皮肤渗透和血液循环过程中发生的转化。比较了微针辅助扩散的皮肤渗透和沉积特性与被动扩散的特性。观察到的数据表明，与被动扩散相比，地塞米松经微针预处理的大鼠皮肤的透皮渗透明显增强，通量和渗透系数显著增加。这种简单的等度 HPLC 方法可有效地用于评价局部/经皮地塞米松制剂的皮肤渗透。
