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开发一种使用液相色谱-质谱法同时测定他扎罗汀和二丙酸倍他米松及其代谢物的简单方法及其在皮肤药代动力学研究中的应用。

Development of a simple method for simultaneous determination of tazarotene and betamethasone dipropionate and their metabolites using LC-MS method and its application to dermatopharmacokinetic study.

作者信息

Li Lingjun, Zhang Mengli, Ma Pengcheng, Qian Kun

机构信息

Chinese Academy of Medical Sciences, Institute of Dermatology, China.

CAMS and PUMC, Institute of Dermatology, China.

出版信息

Biomed Chromatogr. 2019 Aug;33(8):e4557. doi: 10.1002/bmc.4557. Epub 2019 May 16.

DOI:10.1002/bmc.4557
PMID:30990899
Abstract

In our study, a method for the determination for tazarotene and betamethasone dipropionate in human tissue-engineered skin was established. Tazarotene gel, betamethasone dipropionate cream or a combination cream was administered to the skin. Then the skin was taken off at 0.25, 0.75, 1.75, 3, 5, 8, 12, 24, 36, 48 h time points after the residual drug was removed. The concentrations of tazarotene, betamethasone dipropionate and their major metabolites in skin were determined by LC-MS. Tazarotene and tazarotenic acid were detected in the concentration range of 2-200 μg/mL with an LLOQ of 2 μg/mL. Betamethasone dipropionate was detected in the concentration range 0.5-300 μg/mL with an LLOQ of 0.5 μg/mL, and betamethasone was detected at 2-200 μg/mL with an LLOQ of 2 μg/mL. The intra- and inter-day precisions of the four analytes in the skin homogenate were all <15% (RSD, %). The results showed that tazarotene could be metabolized to tazarotenic acid and betamethasone dipropionate could be metabolized to betamethasone in tissue-engineered skin. The results also revealed that this method was suitable for the simultaneous determination of tazarotene, betamethasone dipropionate and their metabolites in tissue-engineered skin.

摘要

在我们的研究中,建立了一种测定人体组织工程皮肤中他扎罗汀和丙酸倍他米松的方法。将他扎罗汀凝胶、丙酸倍他米松乳膏或复方乳膏涂抹于皮肤上。然后在去除残留药物后的0.25、0.75、1.75、3、5、8、12、24、36、48小时时间点取下皮肤。通过液相色谱-质谱法测定皮肤中他扎罗汀、丙酸倍他米松及其主要代谢物的浓度。他扎罗汀和他扎罗汀酸在2-200μg/mL浓度范围内被检测到,定量下限为2μg/mL。丙酸倍他米松在0.5-300μg/mL浓度范围内被检测到,定量下限为0.5μg/mL,倍他米松在2-200μg/mL浓度范围内被检测到,定量下限为2μg/mL。皮肤匀浆中四种分析物的日内和日间精密度均<15%(相对标准偏差,%)。结果表明,在组织工程皮肤中他扎罗汀可代谢为他扎罗汀酸,丙酸倍他米松可代谢为倍他米松。结果还表明,该方法适用于同时测定组织工程皮肤中他扎罗汀、丙酸倍他米松及其代谢物。

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