Lu Yu-Ting, Hu Zhao-Liang, Shao Fang-Xian, Song Min, Hang Tai-Jun
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.
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.
J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Jan 1;1162:122455. doi: 10.1016/j.jchromb.2020.122455. Epub 2020 Nov 28.
Topical tazarotene combined with clindamycin phosphate can significantly improve the adherence and outcomes for the treatment of acne vulgaris than monotherapy, a novel tazarotene (0.05%)/clindamycin phosphate (1.2%) cream is thus developed. However, the pharmacokinetics and potential interaction of tazarotene and clindamycin phosphate in skin when formulated together remain unknown, which should be investigated to assess this novel cream. In the present work, a sensitive and rapid LC-MS/MS method for simultaneous determination of tazarotene, clindamycin phosphate and their active metabolites tazarotenic acid, clindamycin in Bama mini-pig skin was developed and reported for the first time. After pretreatment of the skin samples, the analytes were well separated on a Hypersil BDS C column (4.6 × 100 mm, 2.4 μm) using 0.2% (v/v) formic acid-0.1% (w/v) ammonium acetate water solution and acetonitrile as mobile phase in linear gradient elution. Quantification of tazarotene, clindamycin phosphate and their active metabolites tazarotenic acid, clindamycin was conducted under positive electrospray ionization mode using multiple reactions monitoring detection. The LC-MS/MS method was fully validated and then applied to the dermal pharmacokinetic study of the tazarotene/clindamycin phosphate cream. According to the obtained results, tazarotene and clindamycin phosphate did not have any drug-drug interaction when they were formulated together in the cream for topical application. Their absorption and metabolism features in the skin were also characterized, which can support the clinical medication regimen of tazarotene/clindamycin phosphate cream.
外用他扎罗汀联合磷酸克林霉素治疗寻常痤疮的依从性和疗效显著优于单一疗法，因此研发了一种新型的他扎罗汀（0.05%）/磷酸克林霉素（1.2%）乳膏。然而，他扎罗汀和磷酸克林霉素在制成复方制剂时在皮肤中的药代动力学及潜在相互作用尚不清楚，对此应进行研究以评估这种新型乳膏。在本研究中，首次建立并报道了一种灵敏、快速的LC-MS/MS方法，用于同时测定巴马小型猪皮肤中的他扎罗汀、磷酸克林霉素及其活性代谢产物他扎罗汀酸、克林霉素。皮肤样品经预处理后，采用0.2%（v/v）甲酸-0.1%（w/v）醋酸铵水溶液和乙腈作为流动相，在Hypersil BDS C柱（4.6×100 mm，2.4μm）上进行线性梯度洗脱，各分析物得到良好分离。采用正离子电喷雾电离模式，通过多反应监测检测对他扎罗汀、磷酸克林霉素及其活性代谢产物他扎罗汀酸、克林霉素进行定量分析。该LC-MS/MS方法经过充分验证后应用于他扎罗汀/磷酸克林霉素乳膏的皮肤药代动力学研究。根据所得结果，他扎罗汀和磷酸克林霉素制成外用乳膏时不存在药物相互作用。同时还对它们在皮肤中的吸收和代谢特征进行了表征，可为他扎罗汀/磷酸克林霉素乳膏的临床用药方案提供依据。
