Simultaneous determination of tazarotene, clindamycin phosphate and their active metabolites in Bama mini-pig skin by LC-MS/MS: Application to the development of a tazarotene/clindamycin phosphate cream
Simultaneous determination of tazarotene, clindamycin phosphate and their active metabolites in Bama mini-pig skin by LC-MS/MS: Application to the development of a tazarotene/clindamycin phosphate cream
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DOI：
10.1016/j.jchromb.2020.122455
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发表时间：
2021-01-01
影响因子：
3
通讯作者：
Hang, Tai-jun
中科院分区：
文献类型：
--
作者：
Lu, Yu-ting;Hu, Zhao-liang;Hang, Tai-jun
外用他扎罗汀联合克林霉素磷酸酯治疗寻常痤疮较单药治疗能显著提高患者的依从性和疗效，因此研制了一种新型的他扎罗汀（0.05%）/克林霉素磷酸酯（1.2%）乳膏。然而，他扎罗汀和克林霉素磷酸酯在皮肤中的药代动力学和潜在的相互作用，当配制在一起时仍然未知，这应该进行调查，以评估这种新的霜。本文首次建立了同时测定巴马小型猪皮肤中他扎罗汀、克林霉素磷酸酯及其活性代谢物他扎罗汀酸、克林霉素的LC-MS/MS方法。皮肤样品经预处理后，采用Hypersil BDS C-8色谱柱（4.6 × 100 mm，2.4 μ m），以0.2%（v/v）甲酸-0.1%（w/v）乙酸铵水溶液和乙腈为移动的相，线性梯度洗脱，使待测物得到良好分离。采用多反应监测检测器，在正离子电喷雾电离模式下对他扎罗汀、克林霉素磷酸酯及其活性代谢物他扎罗汀酸、克林霉素进行定量分析。对LC-MS/MS方法进行了充分验证，并将其应用于他扎罗汀/克林霉素磷酸酯乳膏的皮肤药代动力学研究。根据所获得的结果，当他扎罗汀和克林霉素磷酸酯一起配制在用于局部应用的乳膏中时，它们没有任何药物-药物相互作用。同时，研究其在皮肤中的吸收代谢特征，为他扎罗汀/克林霉素磷酸酯乳膏的临床用药提供依据。
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-8 column (4.6 x 100 mm, 2.4 mu m) 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.