Development and validation of an LC-MS/MS method for the determination of adapalene in pharmaceutical forms for skin application

Abstract

The development and validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of adapalene in pharmaceutical forms for skin application were presented in this study. The MS/MS analysis of adapalene was performed by use of three mobile phases, consisted of acetonitrile and a) 0.1 % formic acid, b) 0.1 % trifluoroacetic acid and c) 20 mM ammonium acetate. The strongest signals of parent ion and dominant product ion were obtained in negative mode by use of the mobile phase c). The validation of this method was performed according to the ICH guidelines. Small variations of selected chromatographic parameters (concentration of ammonium acetate, mobile phase composition, column temperature and flow rate) did not affect significantly the qualitative and quantitative system responses, which proved the method's robustness. The method is specific for the determination of adapalene. The linearity was proved in the concentration range of 6.7-700.0 ng mL-1 (r = 0.9990), with limits of detection and quantification of 2.0 and 6.7 ng mL-1 , respectively. The accuracy was confirmed by calculated recoveries (98.4-101.5 %). The precision was tested at three levels: injection repeatability, analysis repeatability and intermediate precision. The calculated relative standard deviations were less than 1, 2 and 3 %, respectively.

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.…”