Challa Purushotham Reddy, K Ramakrishna, K M V Narayana Rao
Inogent Laboratories Limited, IDA, Nacharam, Hyderabad, 500076, India.
GITAM institute of Science and Technology, Visakhapatnam, 530045, India.
Biomed Chromatogr. 2017 Nov;31(11). doi: 10.1002/bmc.4004. Epub 2017 Jun 7.
A gradient LC-MS method was developed for the identification and characterization of degradants of moexipril using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Moexipril was subjected to hydrolysis (acid, base and neutral), oxidation, photolytic and thermal degradation conditions as mentioned in ICH guidelines Q1A (R2). The drug degraded under hydrolysis, oxidation and photolytic conditions, but it was stable under thermal conditions. In total, five degradants were formed and separated on an Agilent XDB C-18 column (4.6 × 150 mm, 5 μm) in a gradient elution method. Four degradants (D1, D2, D4 and D5) under acidic conditions, three degradants (D2, D3 and D4) under basic conditions and three degradants (D1, D4 and D5) under neutral and oxidative stress conditions were formed. In addition, two degradants (D4 and D5) were formed under photolytic stress conditions. To elucidate the structures of degradants, fragmentation of moexipril and its degradants was studied using LC-MS/MS experiments and accurate mass measurements (HRMS) data. The fragment ions in the product ion tandem mass spectra of all the degradants were compared with those of moexipril and assigned the probable structures for the degradants.
开发了一种梯度液相色谱-质谱方法，用于使用液相色谱电喷雾电离串联质谱（LC/ESI-MS/MS）鉴定和表征莫昔普利的降解产物。按照国际人用药品注册技术协调会（ICH）指南Q1A（R2）中所述，使莫昔普利经受水解（酸、碱和中性）、氧化、光解和热降解条件。该药物在水解、氧化和光解条件下会降解，但在热条件下稳定。总共形成了五种降解产物，并采用梯度洗脱法在安捷伦XDB C-18柱（4.6×150mm，5μm）上进行分离。在酸性条件下形成了四种降解产物（D1、D2、D4和D5），在碱性条件下形成了三种降解产物（D2、D3和D4），在中性和氧化应激条件下形成了三种降解产物（D1、D4和D5）。此外，在光解应激条件下形成了两种降解产物（D4和D5）。为了阐明降解产物的结构，使用LC-MS/MS实验和精确质量测量（高分辨质谱，HRMS）数据研究了莫昔普利及其降解产物的裂解情况。将所有降解产物的产物离子串联质谱中的碎片离子与莫昔普利的碎片离子进行比较，并为降解产物指定了可能的结构。
