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Characterization of Dimeric Linkage of rhPTH(1-34) Induced by Heat, Humidity and Light Stress

机译:热,湿度和光应力诱导的rhPth(1-34)二聚体连杆的表征

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The human parathyroid hormone is an 84 amino acid peptide (hPTH (1-84)). hPTH(1-84) and its active forms, such as hPTH (1-34), teriparatide, strongly stimulate bone formation. Lilly markets Forteo. (formulated rhPTH(1-34) to treat osteoporosis. One important characterization strategy during drug development is to investigate drug related substances under stressed conditions for accelerated degradation. Low levels of aggregates (mainly dimer) of rhPTH(1-34) were found when the drug substance was exposed to extreme heat (4 days at 60 deg C/ Ambient Humidity), humidity (4 days at 30 deg C/70%RH) and light (25 deg C/Xenon Lamp (3.3 million lux hours)). This presentation describes an LC/MS/MS-based approach to elucidate the dimeric linkages. The dimer fractions were collected from SEC, either directly treated with trypsin or further fractionated on reverse-phase LC and then treated with trypsin. The digests were analyzed using capillary LC/MS/MS.
机译:人甲状旁腺激素是84个氨基酸肽(HPTH(1-84))。 HPTH(1-84)及其活性形式,如HPTH(1-34),Teriparate,强烈刺激骨形成。 Lilly Markets Forteo。 (配制的rhPth(1-34)治疗骨质疏松症。药物开发期间的一个重要表征策略是在压力条件下调查药物相关物质,以加速降解。rhPth(1-34)的低水平(主要是二聚体)将药物暴露于极端热量(60℃/环境湿度为4天),湿度(30℃/ 70%RH)和光(25℃/氙气灯(330万Lux小时))。该介绍描述了一种基于LC / MS / MS的方法来阐明二聚体连杆。从秒钟中收集二聚体级分,用胰蛋白酶直接处理或在反相LC上进一步分级,然后用胰蛋白酶处理。使用胰蛋白酶处理。使用毛细管LC / MS / MS。

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