Forced Degradation Studies to Assess the Stability of a Janus Kinase Inhibitor Using RPLC Method

Hülya Yılmaz
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引用次数: 1

Abstract

In optimization studies, it is important to study the retention behavior of the compounds containing the ionizable functional groups under the intended chromatographic conditions. In this study, the influence of pH and acetonitrile (ACN) composition in the mobile phase on chromatographic behavior of tofacitinib (TOF), a Janus kinase (JAK) inhibitor, was investigated in details. First, the chromatographic conditions were optimized using retention factors and pKa values. Then, the developed method was used for the stability studies under various stress conditions, and for the estimation of TOF concentration in tablets. Finally, the method was validated using the International Conference on Harmonization (Q2) guidelines and it was successfully used to separate the TOF degradation products. A linearity range, limit of detection and limit of quantification were determined as 2.0-12.0, 0.416, and 1.260 μg/mL, respectively. Between-day and within-day precisions were found to be as 0.290 and 0.462 for 4 μg/mL, respectively. The result indicates that the developed method is rather effective to separate the parent drug from the degradation products.
用RPLC法评价Janus激酶抑制剂的稳定性
在优化研究中,研究含有可电离官能团的化合物在预期色谱条件下的保留行为是很重要的。本研究详细研究了流动相pH和乙腈(ACN)组成对Janus激酶(JAK)抑制剂tofacitinib (TOF)色谱行为的影响。首先,利用保留因子和pKa值对色谱条件进行优化。然后,将该方法应用于不同应力条件下的稳定性研究,并用于片剂中TOF的浓度估算。最后,使用国际协调会议(Q2)指南对该方法进行了验证,并成功地用于分离TOF降解产物。线性范围为2.0 ~ 12.0,检出限为0.416,定量限为1.260 μg/mL。4 μg/mL的日间精密度为0.290,日内精密度为0.462。结果表明,该方法能较好地分离母药和降解产物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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