Žigart Nina, Časar Zdenko
Sandoz Development Center Slovenia, Analytics Department, Lek Pharmaceuticals d.d., SI-1526 Ljubljana, Slovenia.
Faculty of Pharmacy, Chair of Medicinal Chemistry, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia.
ACS Omega. 2020 Jul 9;5(28):17726-17742. doi: 10.1021/acsomega.0c02338. eCollection 2020 Jul 21.
Venetoclax is an emerging drug for the treatment of various types of blood cancers. It was first approved in 2016 for the treatment of relapsed and refractory chronic lymphocytic leukemia. Later, the indications expanded, and multiple research as well as clinical studies are still conducted involving venetoclax. No analytical method for the determination of venetoclax can currently be found in the literature. We developed a mass spectrometry-compatible stability-indicating ultrahigh-performance liquid chromatography (LC) method for venetoclax. The LC method was developed using analytical quality by design principles. The developed method is able to separate venetoclax and its degradation products. The method was validated in the working point where a linearity range was established and accuracy, repeatability, and selectivity were assessed. Venetoclax is the only Bcl-2 protein inhibitor on the market. It is very effective in combinational therapy, so future drug development involving venetoclax may be expected. A stability-indicating method could aid in the development of new pharmaceutical products with venetoclax.
维奈托克是一种用于治疗多种类型血癌的新兴药物。它于2016年首次获批用于治疗复发难治性慢性淋巴细胞白血病。后来，其适应症有所扩大，目前仍有多项关于维奈托克的研究及临床研究正在进行。目前在文献中尚未发现测定维奈托克的分析方法。我们开发了一种用于维奈托克的与质谱兼容的稳定性指示超高效液相色谱（LC）方法。该LC方法是根据质量源于设计原则开发的。所开发的方法能够分离维奈托克及其降解产物。该方法在建立线性范围并评估准确性、重复性和选择性的工作点进行了验证。维奈托克是市场上唯一的Bcl-2蛋白抑制剂。它在联合治疗中非常有效，因此有望开展涉及维奈托克的未来药物研发。一种稳定性指示方法有助于开发含有维奈托克的新药品。
