Identification and structural characterization of hydrolytic degradation products of alvimopan by LC/QTOF/MS/MS and NMR studies

被引：6
作者：
Baira, Shandilya Mahamuni [1 ]
Srinivas, R. [2 ]
Talluri, M. V. N. Kumar [1 ]
机构：
[1] Natl Inst Pharmaceut Educ & Res, Dept Pharmaceut Anal, Hyderabad 500037, Telangana, India
[2] CSIR Indian Inst Chem Technol, Analyt Dept, Hyderabad, Telangana, India
来源：
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS | 2019年 / 165卷
关键词：
Alvimopan; Stress degradation; Degradation products; LC/QTOF/MS/MS; NMR; Characterization; IMPURITIES; METABOLITE;
D O I：
10.1016/j.jpba.2018.12.035
中图分类号：
O65 [分析化学];
学科分类号：
070302 ; 081704 ;
摘要：
Alvimopan (ALV), a peripherally acting mu-opioid receptor (PAM-OR) antagonist used for the treatment of postoperative ileus, was examined for its degradation behaviour under different stress conditions. A total of five degradation products (DP1-DP5) were formed and identified using high-performance liquid chromatography (HPLC) method. Primarily, complete fragmentation pathways of the protonated drug and its degradation products (DP1-DP5) were elucidated by using liquid chromatography-mass spectrometry (LC/MS) and high-resolution mass spectrometry (HRMS) studies. Subsequently, three major degradation products (DP1-DP3) formed under acid hydrolytic stress conditions were isolated by preparative-high performance liquid chromatography (prep-HPLC) and subjected to nuclear magnetic resonance (NMR) experiments (1D and 2D NMR) for further confirmation of their structures. All the spectral data from LC/QTOF/MS/MS and NMR studies were used for the identification and structural characterization of degradation products (DP1-DP5). (C) 2018 Published by Elsevier B.V.
引用
收藏
页码：399 / 409
页数：11
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