Solriamfetol is a novel FDA approved enantiopure drug used for the treatment of excessive sleepiness associated with narcolepsy or obstructive sleep apnea. Only the active R -enantiomer is marketed, therefore, a method to determine the chiral purity is essential. Chiral separation of solriamfetol was performed by HPLC using polysaccharide-type chiral stationary phases in polar organic mode and described for the first time. Seven different polysaccharide-based chiral columns (Lux Amylose-1, Lux i-Amylose-1, Lux Amylose-2, Lux Cellulose-1, Lux Cellulose-2, Lux Cellulose-3 and Lux Cellulose-4) were employed for the separation of enantiomers using polar organic mode, with mobile phases consisting of 0.15% diethylamine in methanol (MeOH), 2-propanol (IPA) or acetonitrile (ACN). During the screening phase, the best results ( R s > 5, in less than 10 min) was obtained on a Lux Amylose-1 column with 0.15% diethylamine in methanol with an ideal elution order (the distomer eluted before the R -enantiomer). The effects of binary mobile phases on the resolutions and retention factors were also investigated containing different percentages of MeOH:ACN and MeOH:IPA. Using optimized parameters (Lux Amylose-1 column with 0.05% diethylamine in MeOH with 0.6 mL/min flow rate at 20 °C) high enantioresolution ( R s = 5.3) was achieved within 6 min. Thermodynamic analysis was performed and revealed an enthalpy-driven enantioseparation. The developed, isocratic HPLC method was validated according to current ICH guidelines and proved to be reliable, linear, precise and accurate for the determination of 0.1% S -enantiomer as a chiral impurity in R -solriamfetol.

中文翻译：

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使用多糖型手性固定相在极性有机模式下通过高效液相色谱法测定 Solriamfetol 的对映体纯度

Solriamfetol 是一种新型 FDA 批准的对映体纯药物，用于治疗与发作性睡病或阻塞性睡眠呼吸暂停相关的过度嗜睡。只有活性R-对映异构体在市场上销售，因此，确定手性纯度的方法是必不可少的。solriamfetol 的手性分离是通过 HPLC 使用多糖型手性固定相在极性有机模式下进行的，并首次被描述。七种不同的基于多糖的手性色谱柱（Lux Amylose-1、Lux i-Amylose-1、Lux Amylose-2、Lux Cellulose-1、Lux Cellulose-2、Lux Cellulose-3 和 Lux Cellulose-4）用于分离使用极性有机模式分析对映异构体，流动相由甲醇 (MeOH)、2-丙醇 (IPA) 或乙腈 (ACN) 中的 0.15% 二乙胺组成。在筛选阶段，最好的结果（R s > 5，在不到 10 分钟的时间内）在 Lux Amylose-1 柱上获得，其中含有 0.15% 二乙胺的甲醇溶液，具有理想的洗脱顺序（在 R-对映体之前洗脱出异构体）。还研究了含有不同百分比的 MeOH:ACN 和 MeOH:IPA 的二元流动相对分辨率和保留因子的影响。使用优化的参数（Lux Amylose-1 色谱柱，含有 0.05% 二乙胺的 MeOH，流速为 0.6 mL/min，20 °C）在 6 分钟内实现了高对映分离度 (R s = 5.3)。进行了热力学分析并揭示了焓驱动的对映分离。开发的等度 HPLC 方法根据当前 ICH 指南进行了验证，并证明其可靠、线性、精确和准确，可用于测定 R-solriamfetol 中作为手性杂质的 0.1% S-对映异构体。