Abstract：
Treprostinil (Remodulin®) is a Food and Drug Administration (FDA) approved prostacyclin analog to treat pulmonary arterial hypertension. Recently, treprostinil has been investigated to reduce ischemia-reperfusion injury (IRI) during transplantation, which currently has no approved treatment. A validated analytical method is necessary to measure treprostinil concentrations in biological specimens. Here, a novel, sensitive, and specific method to measure treprostinil concentrations in rat serum, human serum, and human plasma has been developed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Biological samples were processed by protein precipitation before chromatography and 6-keto Prostaglandin F1α-d4 was used as an internal standard. A gradient method was established with a total run time of 4 min. The assay was linear over the range of 0.25-75.0 ng/ml with accuracy (92.97-107.87 %), intra-assay precision (1.16-3.34 %), and inter-assay precision (1.11-4.58 %) in all biological matrices, which are within FDA acceptance criteria. No significant variation in treprostinil or 6-keto Prostaglandin F1α-d4 concentrations were observed under the investigated storage conditions. This novel, sensitive, and specific LC/MS-MS method is cost-effective and suitable for measuring treprostinil concentrations in animal studies and human biological samples for clinical applications.
摘要：
曲前列环素(Remodulin®)是食品和药物管理局(FDA)批准的前列环素类似物,用于治疗肺动脉高压。最近,已经研究了曲前列环素以减少移植过程中的缺血再灌注损伤（IRI），目前没有治疗。需要一种经过验证的分析方法来测量生物标本中曲前列环素的浓度。这里,一本小说,敏感,和测定大鼠血清中曲前列环素浓度的具体方法，人血清,和人血浆已使用液相色谱-串联质谱（LC-MS/MS）开发。在层析之前通过蛋白质沉淀处理生物样品,并且使用6-酮前列腺素F1a-d4作为内标。建立了总运行时间为4分钟的梯度方法。该测定在0.25-75.0ng/ml的范围内呈线性，准确度（92.97-107.87％），测定内精密度（1.16-3.34%），和所有生物基质的测定间精度(1.11-4.58%)，符合FDA的验收标准。在不同的储存条件下，未观察到曲前列环素或6-酮前列腺素F1α-d4浓度的显着变化。这本小说,敏感,和特定的LC/MS-MS方法具有成本效益，适用于测量动物研究和人类生物样品中曲前列环素的浓度以用于临床应用。
