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

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.

Application of an In Vitro Psoriatic Skin Model to Study Cutaneous Metabolization of Tazarotene

“…To our knowledge, this study is the first to report such metabolic activity in tissue-engineered reconstructed skin models. These results are in accordance with results obtained in vivo where levels similar to 1% of the tazarotene dose was also metabolized into tazarotenic acid [37][38][39]. More tazarotene was found in the epidermis, while tazarotenic acid was found predominantly in the dermis.…”

Quantitative method for determination of 3,3‐dimethylallyl bromide genotoxic impurity in Tazarotene drug substance by GC‐MS

“…High-sensitive HPLC methods were used to quantify the tazarotene; it is process and degradation impurities [5][6][7][8][9]. A high-performance thin-layer chromatography (HPTLC) method was established to determine the tazarotene in topical gel formulations and in vitro study [9], other liquid chromatography-mass spectrometric and gas chromatography-mass spectrometry methods were available to determine tazarotene and its impurities [9][10][11][12][13]. As per author cognizance, no analytical method was available in the literature for determination of 1-bromo-3 methyl -2-butene/3,3-dimethylallyl bromide at a low level (<10 ppm) in presence of tazarotene drug substance and drug product.…”