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Simultaneous Quantification and Pharmacokinetic Study of Five Homologs of Dalbavancin in Rat Plasma Using UHPLC-MS/MS

机译:使用UHPLC-MS / MS的达巴万蛋白五种同源物的同时量化和药代动力学研究

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摘要

Dalbavancin is a novel semisynthetic glycopeptide antibiotic that comprises multiple homologs and isomers of similar polarities. However, pharmacokinetic studies have only analyzed the primary components of dalbavancin, namely B0 and B1. In this study, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to simultaneously determinate and investigate the five homologous components of dalbavancin, namely, A0, A1, B0, B1, and B2, in rat plasma. In this method, methanol was used to precipitate plasma, and a triple-bonded alkyl chromatographic column was used for molecule separation, using 0.1% formic acid-acetonitrile as the mobile phase for gradient elution. Targeted homologs were analyzed by a triple quadrupole mass spectrometer using positive electrospray ionization in multiple reaction monitoring mode. The linearity range was 50–2500 ng/mL with a high correlation coefficient (r2 > 0.998). This method was successfully applied in the pharmacokinetic analysis of dalbavancin hydrochloride to investigate dalbavancin components in rats.
机译:达巴万蛋白是一种新型半合成糖肽抗生素,其包含多种同源物和类似极性的异构体。然而,药代动力学研究仅分析了达巴万蛋白的主要成分,即B0和B1。在该研究中,开发了超高效液相色谱 - 串联质谱(UHPLC-MS / MS)方法以同时测定和研究达巴万蛋白的五种同源组分,即A0,A1,B0,B1和B2 ,在大鼠等离子体中。在该方法中,使用甲醇沉淀等离子体,并且使用三键合烷基色谱柱进行分子分离,使用0.1%甲酸 - 乙腈作为梯度洗脱的流动相。通过多重电气喷雾电离在多重反应监测模式下通过三重四极杆质谱仪分析靶向同源物。线性范围为50-2500ng / ml,具有高相关系数(R2> 0.998)。该方法已成功应用于盐酸达巴达甘司的药代动力学分析,以研究大鼠达巴万武汀组分。

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