稳定性指示方法用于测定拉考沙胺及其降解产物。

Stability-indicating methods for the determination of racecadotril in the presence of its degradation products.

机构信息

Analytical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.

出版信息

Biosci Trends. 2009 Dec;3(6):247-52.

PMID:20103854

Abstract

Three stability-indicating methods were developed for the determination of racecadotril (RCT) in the presence of its alkaline degradation products. The first was an HPLC method in which efficient chromatographic separation was achieved on a C18 analytical column and a mobile phase of acetonitrile-methanol-water-acetic acid (52:28:20:0.1, v/v/v/v). Linearity was obtained in the range of 4-40 microg/mL with mean accuracy of 99.5 +/- 0.88%. The second method was a densitometric evaluation of thin-layer chromatograms of the drug using a mobile phase of isopropanol-ammonia (33%)-n-hexane (9:0.5:20, v/v/v). The chromatograms were scanned at 232 nm, a wavelength at which RCT can be readily separated from its degradation products and determined in the range of 2-20 microg per spot with mean accuracy of 99.5 +/- 0.56%. The third method is based on the use of first-derivative spectrophotometry (D1) at 240 nm, and the drug was determined in the range of 5-40 microg/mL with mean accuracy of 99.2 +/- 1.02%. The three methods provided satisfactory recovery of the intact drug (100.8 +/- 0.82, 100.4 +/- 0.55, and 99.9 +/- 0.72%, respectively) in the presence of up to 90% of its degradation products. Determination was also successful when analyzing RCT in a formulation in the form of acetorphan packets. Results were statistically analyzed and found to be in accordance with those given by a reported method.

摘要

建立了三种用于在其碱性降解产物存在下测定雷卡多曲（RCT）的稳定性指示方法。第一种是 HPLC 方法，在 C18 分析柱上，以乙腈-甲醇-水-乙酸（52:28:20:0.1，v/v/v/v）为流动相，实现了有效的色谱分离。在线性范围内为 4-40 μg/mL，平均准确度为 99.5±0.88%。第二种方法是使用异丙醇-氨水（33%）-正己烷（9:0.5:20，v/v/v）作为流动相，对药物的薄层色谱图进行密度评估。在 232nm 波长下，RCT 可以很容易地与其降解产物分离，并在 2-20μg/斑点范围内进行测定，平均准确度为 99.5±0.56%。第三种方法基于一阶导数分光光度法（D1）在 240nm 处的使用，药物在 5-40μg/mL 范围内进行测定，平均准确度为 99.2±1.02%。这三种方法在高达 90%的降解产物存在下，均能提供满意的完整药物回收率（分别为 100.8±0.82%、100.4±0.55%和 99.9±0.72%）。在以乙酰氨酚包的形式分析 RCT 制剂时，也成功地进行了测定。结果经过统计学分析，与报道的方法给出的结果一致。