Cardoso Priscila Aburachid, Pereira Diego Beltrão, El-Behairy Mohammed Farrag, Ghanem Ashraf, Pianetti Gerson Antônio, César Isabela Costa
Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Chirality Group, Faculty of Science and Technology, University of Canberra, ACT, Australia.
J Chromatogr Sci. 2019 May 1;57(5):443-450. doi: 10.1093/chromsci/bmz014.
Chloroquine is a chiral antimalarial drug and demonstrates enantioselective pharmacodynamic and pharmacokinetic properties. However, this drug is administered as racemate. The knowledge of stereoselective aspects of these agents may be useful to better understand their mechanisms of action and to optimize their safety and/or clinical efficacy. In this study, an enantioselective analytical method for the quantification of chloroquine enantiomers was developed using HPLC-UV. The chromatographic conditions were: Chirobiotic V column (100 × 2.1 mm, 5 μm) at 25°C, mobile phase containing methanol:acetic acid:triethylamine (100:0.12:0.12), flow rate 1 mL/min, injection volume 10 μL and detection at 258 nm. The validation parameters evaluated were selectivity, linearity, precision, accuracy, and robustness. In addition, a stability study after forced degradation of chloroquine enantiomers was performed. The enantioseparation of chloroquine using a polysaccharide-based chiral stationary phase (Chiralpak ID) at different mobile phase composition was evaluated and the chromatographic performance of both columns was compared. Thus, a stability-indicating chiral analytical method was developed and fully validated, allowing the separation of chloroquine enantiomers and its degradation products in tablets available in Brazil.
氯喹是一种手性抗疟药物，具有对映体选择性的药效学和药代动力学特性。然而，该药物是以消旋体形式给药的。了解这些药物的立体选择性方面可能有助于更好地理解其作用机制，并优化其安全性和/或临床疗效。在本研究中，开发了一种使用高效液相色谱-紫外检测法（HPLC-UV）定量氯喹对映体的对映体选择性分析方法。色谱条件为：在25℃下使用Chirobiotic V柱（100×2.1 mm，5μm），流动相为甲醇：乙酸：三乙胺（100:0.12:0.12），流速1 mL/min，进样体积10μL，检测波长258 nm。评估的验证参数包括选择性、线性、精密度、准确度和稳健性。此外，还进行了氯喹对映体强制降解后的稳定性研究。评估了在不同流动相组成下使用多糖基手性固定相（Chiralpak ID）对氯喹进行对映体拆分的情况，并比较了两根柱子的色谱性能。因此，开发并全面验证了一种稳定性指示手性分析方法，该方法能够分离巴西市售片剂中的氯喹对映体及其降解产物。
