Andri B, Dispas A, Klinkenberg R, Streel B, Marini R D, Ziémons E, Hubert Ph
University of Liège (ULg), CIRM, Laboratory of Pharmaceutical Analytical Chemistry, 15 Avenue Hippocrate, B36, B-4000 Liège, Belgium.
University of Liège (ULg), CIRM, Laboratory of Pharmaceutical Analytical Chemistry, 15 Avenue Hippocrate, B36, B-4000 Liège, Belgium.
J Chromatogr A. 2017 Sep 15;1515:209-217. doi: 10.1016/j.chroma.2017.07.057. Epub 2017 Jul 27.
Nowadays, many efforts are devoted to improve analytical methods regarding efficiency, analysis time and greenness. In this context, Supercritical Fluid Chromatography (SFC) is often regarded as a good alternative over Normal Phase Liquid Chromatography (NPLC). Indeed, modern SFC separations are fast, efficient with suitable quantitative performances. Moreover, the hyphenation of SFC to mass spectrometry (MS) provides additional gains in specificity and sensitivity. The present work aims at the determination of vitamin D3 by SFC-MS for routine Quality Control (QC) of medicines specifically. Based on the chromatographic parameters previously defined in SFC-UV by Design of Experiments (DoE) and Design Space methodology, the method was adapted to work under isopycnic conditions ensuring a baseline separation of the compounds. Afterwards, the response provided by the MS detector was optimized by means of DoE methodology associated to desirability functions. Using these optimal MS parameters, quantitative performances of the SFC-MS method were challenged by means of total error approach method validation. The resulting accuracy profile demonstrated the full validity of the SFC-MS method. It was indeed possible to meet the specification established by the European Medicines Agency (EMA) (i.e. 95.0 - 105.0% of the API content) for a dosing range corresponding to at least 70.0-130.0% of the API content. These results highlight the possibility to use SFC-MS for the QC of medicine and obviously support the switch to greener analytical methods.
如今，人们致力于在效率、分析时间和环保性方面改进分析方法。在此背景下，超临界流体色谱法（SFC）常被视为比正相液相色谱法（NPLC）更好的选择。事实上，现代SFC分离速度快、效率高，具有合适的定量性能。此外，SFC与质谱（MS）联用在特异性和灵敏度方面有额外提升。本工作旨在通过SFC-MS测定维生素D3，专门用于药品的常规质量控制（QC）。基于先前通过实验设计（DoE）和设计空间方法在SFC-UV中定义的色谱参数，该方法经过调整以在等密度条件下运行，确保化合物的基线分离。之后，通过与期望函数相关的DoE方法对MS检测器提供的响应进行了优化。使用这些最佳MS参数，通过总误差方法验证对SFC-MS方法的定量性能进行了验证。所得的准确度曲线证明了SFC-MS方法的完全有效性。对于对应于至少70.0 - 130.0%的活性成分含量的给药范围，确实有可能满足欧洲药品管理局（EMA）制定的规范（即活性成分含量的95.0 - 105.0%）。这些结果突出了使用SFC-MS进行药品质量控制的可能性，显然支持转向更环保的分析方法。
