Development and validation of a sensitive and robust chiral method for (R)-propylene oxide: From chiral gas chromatography to chiral liquid chromatography with pre-column derivatization

Journal of chromatography open Pub Date : 2024-05-01 DOI:10.1016/j.jcoa.2024.100141

Brian Lingfeng He, Michelle Kubin, Yueer Shi, Brent Kleintop

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Abstract

Propylene oxide (PO) is an important chemical commodity and a chiral building block to prepare pharmaceutical compounds. It is crucial to develop a sensitive and robust chiral method that can be used to assess the enantiomeric purity of PO and safeguard the quality and safety of pharmaceutical products in commercial quality control (QC) laboratories. A chiral gas chromatography (GC) method based on direct enantioseparation of PO enantiomers on a 50-meter Chiraldex™ A-TA open capillary column was successfully developed for determination of enantiomeric impurity (S)-PO in (R)-PO. However, it was revealed that the chiral GC method lacked adequate robustness for routine use. Consequently, a chiral high-performance liquid chromatography (HPLC) method was developed through pre-column derivatization of PO with 2-naphthalenethiol followed by enantioseparation on a Lux Cellulose-1 (250 mm × 4.6 mm, 5 µm) column. The chiral HPLC method has been demonstrated excellent specificity, sensitivity, accuracy and robustness through method validation and robustness evaluation, thus establishing its suitability for routine use in QC laboratories.

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开发和验证灵敏稳健的 (R)- 环氧丙烷手性方法：从手性气相色谱到柱前衍生化手性液相色谱法

环氧丙烷（PO）是一种重要的化学商品，也是制备医药化合物的手性构件。开发一种灵敏、稳健的手性方法至关重要，该方法可用于评估环氧丙烷对映体的纯度，保障商业质量控制（QC）实验室药品的质量和安全。研究人员成功开发了一种手性气相色谱（GC）方法，该方法基于在 50 米长的 Chiraldex™ A-TA 开放式毛细管柱上直接对 PO 对映体进行对映体分离，以测定 (R)-PO 中的对映体杂质 (S)-PO。然而，研究发现该手性气相色谱方法在日常使用中缺乏足够的稳定性。因此，我们开发了一种手性高效液相色谱（HPLC）方法，先用 2-萘硫醇对 PO 进行柱前衍生，然后在 Lux Cellulose-1（250 mm × 4.6 mm，5 µm）色谱柱上进行对映体分离。通过方法验证和稳健性评估，该手性型高效液相色谱法具有极佳的特异性、灵敏度、准确性和稳健性，因此适合质控实验室的常规使用。

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