Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, China; Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China.
Institute of Dermatology and Hospital for Skin Disease, Chinese Academy of Medical Sciences & Peking Union Medical Collage, Nanjing, China.
J Pharm Biomed Anal. 2020 Jul 15;186:113322. doi: 10.1016/j.jpba.2020.113322. Epub 2020 Apr 23.
Tazarotene and clobetasol propionate are efficacious for the treatment of psoriasis. The plasma pharmacokinetic assessments of tazarotene or clobetasol propionate have been reported. However, the pharmacokinetic characteristics of tazarotene and clobetasol propionate in skin when used together have not been studied. In the present study, sensitive and rapid methods were developed for the determination of clobetasol propionate, tazarotene and its active metabolite tazarotenic acid in Bama mini-pig skin by UPLC-MS/MS. After homogenization and pretreatment of skin samples, the separation was performed on a WondaSiL C column (4.6 × 150 mm, 5 μm) for tazarotene and clobetasol propionate. The separation of tazarotenic acid was achieved on a BDS HYPERSIL C column (4.6 × 100 mm, 2.4 μm). All the analytes were quantified with positive electrospray ionization and multiple reactions monitoring mode. The assay was validated in the range of 22-1111 ng/g for tazarotene and clobetasol propionate, 2-111 ng/g for tazarotenic acid in skin samples. The methods were fully validated to meet the requirements for bioassay in accuracy, precision, recovery, reproducibility, stabilities and matrix effects, and successfully applied to evaluate the novel combination ointment of tazarotene and clobetasol propionate. The obtained intradermal content-time curves characterized the dermal absorption and metabolism features of the combination ointment. It was also found that there was no significant drug-drug interaction trend between tazarotene and clobetasol propionate. The obtained results would be essential for the development and clinical applications of this novel combination ointment.
他扎罗汀和丙酸氯倍他索均可有效治疗银屑病。已有关于他扎罗汀或丙酸氯倍他索的血浆药代动力学评估的报道。然而，尚未研究联合使用时他扎罗汀和丙酸氯倍他索在皮肤中的药代动力学特征。本研究建立了超高效液相色谱串联质谱法同时测定巴马小型猪皮肤中丙酸氯倍他索、他扎罗汀及其活性代谢物他扎罗汀酸的方法。皮肤样品经匀浆和预处理后，采用 WondaSiL C 柱（4.6×150mm，5μm）分离他扎罗汀和丙酸氯倍他索，采用 BDS HYPERSIL C 柱（4.6×100mm，2.4μm）分离他扎罗汀酸。所有分析物均采用正电喷雾电离和多反应监测模式进行定量分析。该方法在他扎罗汀和丙酸氯倍他索的 22-1111ng/g、皮肤中他扎罗汀酸的 2-111ng/g范围内进行验证。该方法经充分验证，符合准确度、精密度、回收率、重现性、稳定性和基质效应的生物测定要求，并成功应用于评价他扎罗汀和丙酸氯倍他索的新型复方软膏。所得的皮内含量-时间曲线表征了该复方软膏的皮肤吸收和代谢特征。还发现他扎罗汀和丙酸氯倍他索之间没有明显的药物相互作用趋势。这些结果对于该新型复方软膏的开发和临床应用至关重要。
