Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche and Drug and Food Biotechnology Center, Università degli Studi del Piemonte Orientale Amedeo Avogadro, Via Bovio 6, 28100 Novara, Italy.
J Pharm Biomed Anal. 2010 Apr 6;51(5):1024-31. doi: 10.1016/j.jpba.2009.10.026. Epub 2009 Nov 6.
A stability-indicating high-performance liquid chromatography procedure has been developed for the determination of alizapride (AL) and its main degradation products alizapride carboxylic acid (AL-CA) and alizapride N-oxide (AL-NO2) in drug substance and product. The method was developed based on forced degradation data obtained by HPLC-MS analysis. Indeed AL underwent chemical degradation by acid/base catalyzed hydrolysis and oxidation the main degradation products being AL-CA and AL-NO2 respectively. The separation and quantisation were achieved on a 150-mm reverse phase column with a hydrophilic linkage between silica particles and hydrophobic alkyl chains. The mobile phase was constituted (flow rate 1.5mLmin(-1)) of eluant A: aqueous acetate buffer (pH 4.0; 20mM) and eluant B: CH(3)OH using a gradient elution and detection of analytes at 225nm. The method showed good linearity for the AL, AL-CA, AL-NO2 mixture in the 25-75, 1-15 and 1-15microgmL(-1) ranges respectively, being all the square of the correlation coefficients greater than 0.999. The precision, determined in terms of intra-day and inter-day precisions and expressed as RSDs were 0.8, 1.3 and 2.1% and 1.0, 1.7, 4.8% for AL, AL-CA and AL-NO2 respectively. The method demonstrated also to be accurate; indeed the average recoveries, at 100% and 0.2% of the target assay concentration, were 100.5, 98.6, and 96.8% for AL, AL-CA and AL-NO2 respectively. The robustness was also evaluated by variations of mobile phase composition and pH. Finally, the applicability of the method was evaluated in commercial dosage form analysis as well as in stability studies.
已开发出一种用于测定原料药和制剂中阿立必利（AL）及其主要降解产物阿立必利羧酸（AL-CA）和阿立必利 N-氧化物（AL-NO2）的稳定性指示高效液相色谱法。该方法是基于 HPLC-MS 分析获得的强制降解数据开发的。事实上，AL 经历了酸碱催化水解和氧化的化学降解，主要降解产物分别为 AL-CA 和 AL-NO2。分离和定量是在 150mm 反相柱上实现的，该柱的硅颗粒和疏烷基链之间具有亲水键合。流动相由洗脱剂 A（pH 4.0 的乙酸盐缓冲液，20mM）和洗脱剂 B（CH3OH）组成（流速为 1.5mLmin(-1))，采用梯度洗脱，在 225nm 处检测分析物。该方法在 25-75、1-15 和 1-15μgmL(-1)范围内对 AL、AL-CA 和 AL-NO2 混合物均显示出良好的线性，相关系数的平方均大于 0.999。精密度以日内和日间精密度表示，RSD 分别为 0.8、1.3 和 2.1%，AL、AL-CA 和 AL-NO2 的分别为 1.0、1.7 和 4.8%。该方法还表现出准确性；实际上，在 100%和 0.2%目标分析浓度下，AL、AL-CA 和 AL-NO2 的平均回收率分别为 100.5、98.6 和 96.8%。通过改变流动相组成和 pH 值对稳健性进行了评估。最后，评估了该方法在商业制剂分析以及稳定性研究中的适用性。
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