Ferreira-Nunes Ricardo, Ferreira Larissa A, Gratieri Tais, Cunha-Filho Marcilio, Gelfuso Guilherme M
Laboratory of Food, Drugs and Cosmetics (LTMAC), School of Health Sciences, University of Brasília, Brasília, DF, Brazil.
Biomed Chromatogr. 2019 Nov;33(11):e4656. doi: 10.1002/bmc.4656. Epub 2019 Aug 20.
A simple, stability-indicating, chromatographic method of quantifying spironolactone (SPI) and its metabolite, canrenone (CAN), in the presence of excipients typical in dermatological formulations and skin matrices in studies of passive and iontophoretic permeation was proposed and validated here. SPI and CAN were separated using a reversed-phase column with a mobile phase of methanol-water (60:40, v/v) at a flow rate of 1.0 mL/min. Data were collected with a UV detector at 238 and 280 nm, with retention times of 6.2 and 7.9 min for SPI and CAN, respectively. The method was precise, accurate and linear (r > 0.99) in a concentration range of 1-30 μg/mL, and recovery rates of SPI and CAN from the different skin layers exceeded 85%. The method was not only sensitive (LOD of 0.05 and 0.375 μg/mL and LOQ of 0.157 and 1.139 μg/mL for SPI and CAN, respectively) but also selective against skin matrices and highly representative components of topical formulations. The method moreover demonstrated SPI's degradation in iontophoresis by applying Pt-AgCl electrodes and its continued drug stability using Ag-AgCl electrodes. Altogether, the method proved valuable for quantifying SPI and CAN and may be applied in developing and controlling the quality of dermatological products.
本文提出并验证了一种简单的、稳定性指示色谱法，用于在被动和离子导入渗透研究中，在皮肤科制剂和皮肤基质中典型辅料存在的情况下，对螺内酯（SPI）及其代谢物坎利酮（CAN）进行定量分析。使用反相柱，以甲醇 - 水（60:40，v/v）为流动相，流速为1.0 mL/min，分离SPI和CAN。用紫外检测器在238和280 nm处收集数据，SPI和CAN的保留时间分别为6.2和7.9分钟。该方法在1 - 30 μg/mL的浓度范围内精确、准确且呈线性（r > 0.99），SPI和CAN从不同皮肤层的回收率超过85%。该方法不仅灵敏（SPI和CAN的检测限分别为0.05和0.375 μg/mL，定量限分别为0.157和1.139 μg/mL），而且对皮肤基质和局部制剂的高代表性成分具有选择性。此外，该方法通过应用Pt - AgCl电极证明了SPI在离子导入中的降解，并通过Ag - AgCl电极证明了其持续的药物稳定性。总之，该方法被证明对定量SPI和CAN有价值，可应用于皮肤科产品的开发和质量控制。
