Istituto Superiore di Sanità, Dipartimento del Farmaco, Viale Regina Elena 299, I-00161 Rome, Italy.
J Pharm Biomed Anal. 2010 Sep 5;52(5):665-71. doi: 10.1016/j.jpba.2010.02.021. Epub 2010 Feb 23.
Analytical and semipreparative high-performance liquid chromatography (HPLC) enantioseparation of the proton-pump inhibitor omeprazole (OME) and its potential organic chiral impurities were accomplished on the immobilised-type Chiralpak IA chiral stationary phase (CSP) under both polar organic and normal-phase conditions. The (S)-enantiomers were isolated with a purity of >99% ee and their absolute configuration was empirically assigned by circular dichroism (CD) spectroscopy. A chemo- and enantioselective HPLC method was validated to control the enantiomeric purity of the (S)-enantiomer of OME (ESO), an active ingredient contained in drug products, in the presence of chiral and achiral related substances. The precision, linearity and accuracy of the determination of the (R)-impurity as well as the recovery of ESO from a pharmaceutical preparation were determined. The proposed method uses the mixture methyl tert-butylether (MtBE)-ethyl acetate (EA)-ethanol (EtOH)-diethylamine (DEA) 60:40:5:0.1 (v/v/v/v) as a mobile phase. In these conditions, linearity over the concentration range 0.5-25 microg/ml for (R)-enantiomer was obtained. The limits of detection and quantification were 99 and 333 ng/ml, respectively. The intra and inter-day assay precision was less than 2% (RSD%).
采用手性固定相 Chiralpak IA 对质子泵抑制剂奥美拉唑（OME）及其潜在的有机手性杂质进行了分析型和半制备型高效液相色谱（HPLC）对映体拆分。在极性有机相和正相条件下，（S）-对映体的纯度均大于 99% ee，其绝对构型通过圆二色（CD）光谱经验确定。建立了一种对映选择性 HPLC 方法，以控制药物产品中 OME（ESO）的（S）-对映体的对映体纯度，ESO 是一种活性成分。该方法还测定了（R）-杂质的精密度、线性和准确度以及从药物制剂中回收 ESO 的情况。该方法采用混合流动相甲基叔丁基醚（MtBE）-乙酸乙酯（EA）-乙醇（EtOH）-二乙胺（DEA）60:40:5:0.1（v/v/v/v）。在这些条件下，（R）-对映体在 0.5-25 μg/ml 浓度范围内具有线性。检测限和定量限分别为 99 和 333 ng/ml。日内和日间测定精密度均小于 2%（RSD%）。
