Ferretti Rosella, Carradori Simone, Guglielmi Paolo, Pierini Marco, Casulli Adriano, Cirilli Roberto
Centro nazionale per il controllo e la valutazione dei farmaci, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Rome, Italy.
Dipartimento di Farmacia, Università "G. D'Annunzio" di Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
J Pharm Biomed Anal. 2017 Jun 5;140:38-44. doi: 10.1016/j.jpba.2017.03.021. Epub 2017 Mar 16.
Direct HPLC separation of the enantiomers of triclabendazole sulfoxide (TCBZ-SO), which is the main metabolite of the anthelmintic drug triclabendazole, was carried out using the polysaccharide-based Chiralpak AS-H and Chiralpak IF-3 chiral stationary phases (CSPs). The chromatographic behaviour of both CSPs was evaluated and compared using normal-phase and reversed-phase eluents at different column temperatures. The eluent mixture of n-hexane-2-propanol-trifluoroacetic acid 70:30:0.1 (v/v/v) and a column temperature of 40°C were identified as the best operational conditions to carry out semipreparative enantioseparations on a 1-cm I.D. AS-H column. Under these conditions, 12.5mg of racemic sample were resolved in a single chromatographic run within 15min. Comparison of calculated and experimental chiroptical properties provided the absolute configuration assignment at the sulfur atom. The salification of the isolated enantiomers of TCBZ-SO by reaction with sodium hydroxide solution produced water-soluble Na salts which are potentially useful in the development of new anthelmintic enantiomerically pure formulations.
使用基于多糖的Chiralpak AS-H和Chiralpak IF-3手性固定相（CSP）对驱虫药三氯苯达唑的主要代谢产物三氯苯达唑亚砜（TCBZ-SO）的对映体进行了直接高效液相色谱分离。使用正相和反相洗脱剂在不同柱温下评估并比较了两种CSP的色谱行为。已确定正己烷-2-丙醇-三氟乙酸70:30:0.1（v/v/v）的洗脱剂混合物和40°C的柱温是在1厘米内径的AS-H柱上进行半制备对映体分离的最佳操作条件。在这些条件下，12.5毫克外消旋样品在15分钟内通过一次色谱运行得到分离。计算得到的和实验测得的旋光性质的比较确定了硫原子处的绝对构型。通过与氢氧化钠溶液反应使分离得到的TCBZ-SO对映体成盐，生成了水溶性钠盐，这些钠盐可能有助于开发新的驱虫对映体纯制剂。
