This study reports a rapid and low-cost LC method for control of enantiomeric purity of duloxetine. Though duloxetine, as marketed and administered, is expected to be a single (S)-enantiomer, the analysis of a few commercial branded samples by the method developed and presented here showed that they contain a relatively high percentage of (R)-enantiomer (e.g., 2.71–5.42%, which is undesirable in drug formulations). A new chiral derivatizing reagent [isatinyl-(S)-naproxen amide] was synthesized on (S)-naproxen platform. Diastereomeric derivatives were synthesized under microwave irradiation and were separated using reversed-phase-HPLC on a C₁₈ column. A combination of acetonitrile and triethylammonium phosphate buffer (9 mM, pH 4) as the mobile phase and detection at 273 nm were found successful. The diastereomeric derivatives at preparative scale were separated using open column chromatography, and the native enantiomers were obtained and characterized. The HPLC separation method was validated for detection limit, linearity, accuracy, and precision. The limits of detection of (S,R)-diastereomer and (S,S)-diastereomer were found to be 12 and 16 pg/mL, respectively, for the 20-μL injected volume. The method so developed has a practical significance and greater societal impact in establishing the control of enantiomeric purity and in ensuring the enantiomeric purity of the drug meant for human consumption.

中文翻译：

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使用一种新的手性试剂和对映体回收率的反相 HPLC 对映体分离和度洛西汀对映体纯度的控制

本研究报告了一种用于控制度洛西汀对映体纯度的快速且低成本的 LC 方法。尽管度洛西汀在市场上销售和给药时预计是单一的 ( S )-对映异构体，但通过本文开发和介绍的方法对一些商业品牌样品的分析表明，它们含有相对较高百分比的 ( R )-对映异构体（例如，2.71–5.42%，这在药物配方中是不受欢迎的）。在( S )-萘普生平台上合成了一种新的手性衍生试剂[靛红-( S )-萘普生酰胺] 。_{在微波辐射下合成非对映异构体衍生物，并在 C 18}上使用反相 HPLC 进行分离柱子。发现乙腈和磷酸三乙铵缓冲液（9 mM，pH 4）的组合作为流动相并在 273 nm 处检测是成功的。使用开放柱色谱分离制备规模的非对映异构体衍生物，并获得天然对映异构体并进行表征。对 HPLC 分离方法的检测限、线性、准确度和精密度进行了验证。( S , R )-非对映体和 ( S , S )的检测限对于 20-μL 的进样量，发现 )-非对映异构体分别为 12 和 16 pg/mL。所开发的方法在建立对映体纯度的控制和确保供人类食用的药物的对映体纯度方面具有实际意义和更大的社会影响。