NMR reveals an undeclared constituent in custom synthetic peptides
NMR reveals an undeclared constituent in custom synthetic peptides
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DOI：
10.1016/j.jpba.2019.112915
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发表时间：
2020-01-30
影响因子：
3.4
通讯作者：
Pauli, Guido F.
中科院分区：
文献类型：
--
作者：
Choules, Mary P.;Bisson, Jonathan;Pauli, Guido F.
而通用的，基于LC的药物控制质量程序在很大程度上取决于检测模式，并可以特别是“盲目”的某些杂质，NMR是一个更通用的，因此，往往更明智的检测器。虽然掺假对全球（在线）市场上销售的活性药物成分（API）和成品的分析提出了不断发展的挑战，研究化学品通常是可信的，而不是被认为是有缺陷的，甚至是掺假的。这份报告显示了核磁共振分析如何发现大量甘露醇的意外存在（20和43% w/w）作为两种定制合成肽DR和DRVYI中的未申报成分，这两种合成肽是商业来源的。即使在60 MHz台式仪器上，定量H-1 NMR（qHNMR）也容易检测到污染物，并对高极性和UV透明的掺杂物进行定量。量子力学H-1迭代全自旋分析（HiFSA）不仅实现了甘露醇和肽的明确鉴定，而且还证实了定量结果。案例表明，在制药和研究QC中，实验验证取代了信任。他们还强调了已建立的高场和最近重新发展的低场台式qHNMR的前景。意外的发现提醒制造商和研究人员，包括/执行NMR和qNMR的优势与常规CNOAA文件和/或研究级化学品的验证。特别是当联合进行时，这可以大大提高研究的信心，并有助于简化制药QC工具箱。(C)2019 Elsevier B. V.版权所有。
Whereas generic, LC-based pharmaceutical control quality procedures depend largely on the detection mode and can be particularly 'blind' to certain impurities, NMR is a more versatile and, thus, often more judicious detector. While adulteration presents ever-evolving challenges for the analysis of active pharmaceutical ingredients (APIs) and finished products sold in the worldwide (online) marketplace, research chemicals are usually trusted rather than being considered flawed or even adulterated.This report shows how NMR analysis uncovered the unanticipated presence of substantial amounts of mannitol (20 and 43% w/w) as undeclared constituent in two custom synthetic peptides, DR and DRVYI, that were sourced commercially. Quantitative H-1 NMR (qHNMR) readily detected the contaminant, even on a 60 MHz benchtop instrument, and quantified the highly polar and UV-transparent adulterant. Quantum-mechanical H-1 iterative Full Spin Analysis (HiFSA) not only achieved unambiguous identification of both the mannitol and the peptides, but also confirmed the quantitative results.The cases show that experimental verification supersedes trust in both pharmaceutical and research QC. They also highlight the promising utility of both established high-field and recently re-evolving low-field benchtop qHNMR. The unanticipated findings remind manufacturers and researchers alike about the advantages of including/performing NMR and qNMR with routine CofA documentation and/or verification of research grade chemicals. Especially when done jointly, this can greatly improve confidence in research and help streamline the pharmaceutical QC toolbox. (C) 2019 Elsevier B.V. All rights reserved.