Chemical Stability of the Botanical Drug Substance Crofelemer: A Model System for Comparative Characterization of Complex Mixture Drugs.
Chemical Stability of the Botanical Drug Substance Crofelemer: A Model System for Comparative Characterization of Complex Mixture Drugs.
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DOI：
10.1016/j.xphs.2017.06.022
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发表时间：
2017-11
影响因子：
3.8
通讯作者：
Schöneich C
中科院分区：
文献类型：
--
作者：
Hewarathna A;Mozziconacci O;Nariya MK;Kleindl PA;Xiong J;Fisher AC;Joshi SB;Middaugh CR;Forrest ML;Volkin DB;Deeds EJ;Schöneich C
作为第二个3部分的系列文章在这个问题上，关于一个数学模型的发展，比较表征复杂的混合物药物使用crofelemer（CF）作为模型化合物，这项工作的重点是CF的化学稳定性的评价。CF是一种生物聚合物，含有原花青素低聚物的混合物，其主要由儿茶素和少量儿茶素组成。对从制剂中提取的CF进行基于分子量的分馏和硫解。选择温度强制降解和金属催化氧化进行加速和强制降解研究。对强制降解CF样品进行分子分级、硫解，并采用负离子电喷雾电离质谱（ESI-MS）和反相HPLC结合UV吸收和荧光检测进行分析。我们进一步分析了使用数据挖掘和机器学习方法从反相HPLC-UV和ESI-MS生成的各种CF样品的化学稳定性数据集。特别是，基于ESI-MS分析数据集中超过800，000个数据点的互信息的计算揭示了在特定储存/降解条件下差异生成的特定CF裂解和降解产物，其最初未使用ESI-MS结果的传统分析进行鉴定。
As the second of a 3-part series of articles in this issue concerning the development of a mathematical model for comparative characterization of complex mixture drugs using crofelemer (CF) as a model compound, this work focuses on the evaluation of the chemical stability profile of CF. CF is a biopolymer containing a mixture of proanthocyanidin oligomers which are primarily composed of gallocatechin with a small contribution from catechin. CF extracted from drug product was subjected to molecular weight—based fractionation and thiolysis. Temperature stress and metal-catalyzed oxidation were selected for accelerated and forced degradation studies. Stressed CF samples were size fractionated, thiolyzed, and analyzed with a combination of negative-ion electrospray ionization mass spectrometry (ESI-MS) and reversed-phase-HPLC with UV absorption and fluorescence detection. We further analyzed the chemical stability data sets for various CF samples generated from reversed-phase-HPLC-UV and ESI-MS using data-mining and machine learning approaches. In particular, calculations based on mutual information of over 800,000 data points in the ESI-MS analytical data set revealed specific CF cleavage and degradation products that were differentially generated under specific storage/degradation conditions, which were not initially identified using traditional analysis of the ESI-MS results.
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影响因子：
2.9
作者：
Crutchley, Rustin D.;Miller, Jennifer;Garey, Kevin W.
通讯作者：
Garey, Kevin W.
影响因子：
3.3
作者：
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通讯作者：
Pihlaja, Kalevi
影响因子：
8.8
作者：
Chen, Liang;Yuan, Pulong;Li, Yiming
通讯作者：
Li, Yiming
影响因子：
3.8
作者：
Jeong, WS;Kong, ANT
通讯作者：
Kong, ANT
影响因子：
6.1
作者：
Crozier, A;Lean, MEJ;Black, C
通讯作者：
Black, C