Simultaneous determination of chiral and achiral impurities of ivabradine on a cellulose tris(3-chloro-4-methylphenylcarbamate) chiral column using polar organic mode
Simultaneous determination of chiral and achiral impurities of ivabradine on a cellulose tris(3-chloro-4-methylphenylcarbamate) chiral column using polar organic mode
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DOI：
10.1016/j.jpba.2019.112851
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发表时间：
2020-01-01
影响因子：
3.4
通讯作者：
Szabo, Zoltan-Istvan
中科院分区：
文献类型：
--
作者：
Ferencz, Elek;Kovacs, Bela;Szabo, Zoltan-Istvan
建立了高效液相色谱法同时测定其有关物质的方法（R-伊伐布雷定、脱氢-S-伊伐布雷定、N-去甲基-S-伊伐布雷定、（（S）-3，4-二甲氧基-双环[4.2.0]辛-1，3，5-三烯-7-基-甲基）-甲胺）和1-（7，8-二甲氧基-1，3，4，5-四氢-2H-3-苯并氮杂卓-2-酮-3-基）-3-氯-丙烷）。考察了7种不同多糖型手性色谱柱（Lux Amylose-1、Lux i-Amylose-1、Lux Amylose-2、Lux Cellulose-1、Lux Cellulose-2、Lux Cellulose-3和Lux Cellulose-4）的分离能力，其中移动的流动相由0.1%二乙胺的甲醇、2-丙醇和乙腈组成。在洗脱实验期间，在Lux Cellulose-2（基于纤维素三（3-氯-4-甲基苯基氨基甲酸酯）色谱柱和甲醇上获得了最佳结果，理想情况下，所有杂质均在S-伊伐布雷定峰之前洗脱。通过全析因筛选设计优化色谱参数（流速、温度和移动的相组分）。使用优化的参数（Lux Cellulose-2柱，具有0.06%（v/v）二乙胺的甲醇/乙腈98/2（v/v）溶液，具有0.45 ml/min的甲醇/乙腈），在20 ℃下，用100 ml/min的乙腈洗脱。在12 ℃下的最小流速）在所有化合物之间实现基线分离。根据人用药品注册技术要求国际协调理事会Q2（R1）指导原则对优化方法进行了验证，证明该方法具有可靠性、线性、精密度和准确度，可用于测定S-伊伐布雷定样品中至少0.05%的所有杂质。在商业片剂处方中检测了方法应用，证明其适用于S-伊伐布雷定手性和非手性有关物质的常规质量控制。(C)2019年，任作家。出版社：Elsevier B.V
A high performance liquid chromatographic method was developed for the simultaneous determination of the related substances (R-ivabradine, dehydro-S-ivabradine, N-demethyl-S-ivabradine, ((S)-3,4-dimethoxy-bicyclo[4.2.0]octa-1,3,5-triene-7-yl-methyl)-methyl-amine) and 1-(7,8-dimethoxy1,3,4,5-tetrahydro-2H-3-benzazepine-2-on-3-y1)-3-chloro-propane) of the heart-rate lowering drug, ivabradine. The separation capability of seven different polysaccharide-type 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) was investigated with a mobile phase consisting of 0.1% diethylamine in methanol, 2-propanol and acetonitrile. During the screnning experiments the best results were obtained on Lux Cellulose-2 (based on cellulose tris(3-chloro-4-methylphenylcarbamate) column with methanol with an ideal case, where all the impurities eluted before the S-ivabradine peak. Chromatographic parameters (flow rate, temperature and mobile phase constituents) were optimized by a full factorial screening design. Using optimized parameters (Lux Cellulose-2 column with 0.06% (v/v) diethylamine in methanol/acetonitrile 98/2 (v/v) with 0.45 mi./min flow rate at 12 degrees C) baseline separations were achieved between all compounds. The optimized method was validated according to the International Council on Harmonization Q2(R1) guideline and proved to be reliable, linear, precise and accurate for determination of at least 0.05% for all impurities in S-ivabradine samples. Method application was tested on a commercial tablet formulation and proved to be suitable for routine quality control of both chiral and achiral related substances of S-ivabradine. (C) 2019 The Authors. Published by Elsevier B.V