Chemistry Department, Aalen University, Aalen, Germany.
Anal Bioanal Chem. 2011 Sep;401(4):1365-75. doi: 10.1007/s00216-011-5183-0. Epub 2011 Jul 6.
Tetracosactide is a synthetic peptide analogue of the human adrenocorticotropic hormone that stimulates the production of cortisol in the adrenal cortex. The medical use of the compound is primarily the diagnosis of the adrenal cortex function. In order to characterize impurities of the drug, tetracosactide samples were analysed by both liquid chromatography and capillary electrophoresis coupled to a quadrupole time-of-flight mass spectrometer. The identification of the impurities was carried out based on accurate mass determination and fragment ion spectra. The presence of several peptides of lower and higher masses than tetracosactide could be shown, including N- and C-terminally truncated peptides as well as peptides which still contained protecting groups or additional amino acids. Furthermore, a semi-quantitative estimation of the relative amounts of the impurities in different samples as well as a commercial preparation revealed that the number and the type of the impurities varied between the samples. Comparing the selectivity of liquid chromatography and capillary electrophoresis regarding the separation of tetracosactide impurities, it can be stated that capillary electrophoresis showed a higher suitability for the separation of tetracosactide fragments (smaller peptides) while the larger peptides, i.e. those wearing protecting groups, were separated more efficiently by liquid chromatography.
促皮质素是一种合成的人促肾上腺皮质激素肽类似物，可刺激肾上腺皮质产生皮质醇。该化合物的主要医学用途是诊断肾上腺皮质功能。为了表征药物的杂质，使用液相色谱和毛细管电泳与四极杆飞行时间质谱仪联用的方法分析了促皮质素样品。通过精确质量测定和碎片离子谱对杂质进行了鉴定。可以证明存在几种比促皮质素低和高的质量的肽，包括 N-和 C-末端截断的肽以及仍含有保护基团或额外氨基酸的肽。此外，对不同样品以及商业制剂中杂质的相对含量进行了半定量估计，结果表明杂质的数量和类型在样品之间有所不同。比较了液相色谱和毛细管电泳在分离促皮质素杂质方面的选择性，可以说毛细管电泳在分离促皮质素片段（较小的肽）方面表现出更高的适用性，而更大的肽，即那些带有保护基团的肽，则通过液相色谱更有效地分离。
