化学
色谱法
赛马鲁肽
串联质谱法
质谱法
液相色谱-质谱法
衍生化
肽
高效液相色谱法
生物化学
医学
利拉鲁肽
2型糖尿病
糖尿病
内分泌学
作者
Baole Zhang,Wanglong Xu,Chuanlong Yin,Yangming Tang
标识
DOI:10.1016/j.jpba.2022.115164
摘要
Under the guideline issued by Food and Drug Administration (FDA), ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin Guidance for Industry, a synthetic Semaglutide that is intended to be a "generic" of the approved rDNA origin Semaglutide is under exploring. Thus, each peptide-related impurity that is 0.10% of the drug substance or greater need to be identified for Semaglutide covered by this guidance. Among others, characterization of the low-level D-amino acid (D form) isomeric impurities are always the most challenging ones. Reverse-phase high-performance liquid chromatography (RP-UPLC) was used to separate the impurities, followed by high resolution mass spectrometry (HRMS) to determine the molecular weight of the impurities that existed in both formulations. Following the targeted D form isomers off-line collection, the samples went through lyophilization, deuterated hydrochloric acid (D-HCl) hydrolyzation with low level D/L form shifting suppression substrates, chiral derivatization and RP-UPLC tandem mass spectrometry analysis of different amino acids by comparing with standards. Herein, we reported an accurate, straightforward characterization method with low limit of detection for the low-level D-Ser8, D-His1 and D-Asp9 Semaglutide impurities in Semaglutide formulations. The developed UPLC tandem HRMS method entails a valuable step forward in the detection of trace levels of the D-isomers of Semaglutide and other peptide products.
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