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采用新型简单灵敏的超高效液相色谱法测定头孢曲松的药代动力学。

Ceftriaxone pharmacokinetics by new simple and sensitive ultra-high-performance liquid chromatography method.

作者信息

Campos Michel Leandro, de Moura Alonso Juliana, Dos Santos Martins Evelin, Oliveira Jonata Augusto, Hussni Carlos Alberto, Peccinini Rosângela Gonçalves

机构信息

Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, UNESP-Univ Estadual Paulista, Araraquara, Sao Paulo, Brazil.

Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science, UNESP-Univ Estadual Paulista, Botucatu, Sao Paulo, Brazil.

出版信息

Diagn Microbiol Infect Dis. 2017 May;88(1):95-99. doi: 10.1016/j.diagmicrobio.2017.02.012. Epub 2017 Feb 27.

DOI:10.1016/j.diagmicrobio.2017.02.012
PMID:28291630
Abstract

Ceftriaxone is a cephalosporin antibiotic with a potent antimicrobial activity and excellent penetration in most body fluids such as pleural, peritoneal, spinal and brain. These facts contribute to the application of ceftriaxone in the treatment of bacterial peritonitis, an abdominal disorder in veterinary medicine, with potential risk of death. The determination of ceftriaxone levels in plasma and peritoneal fluid may be used to assess the pharmacokinetic profile at various instances of administration and allows observing if the concentrations needed are being achieved. Therefore a method was developed and validated for the determination of ceftriaxone in plasma and peritoneal fluid which after was applied in a pharmacokinetic profile study. The bioanalytical method validation was performed according to widely acceptable experiments. Two horses were used as a model of the method applicability; ceftriaxone was intraperitoneally administered to these animals as a single dose. The plasma and peritoneal fluid analysis were performed using an UHPLC system in reverse phase chromatography mode in fully validated conditions. The methods have shown linearity between 0.49 and 500μg/mL for plasma, and between 0.24 and 500μg/mL for peritoneal fluid. The quantitative analysis of ceftriaxone in these matrices allows monitoring of the therapy. This method showed improved sensitivity as well as the quantitation in peritoneal fluid.

摘要

头孢曲松是一种头孢菌素类抗生素,具有强大的抗菌活性,在胸膜、腹膜、脊髓和脑等大多数体液中具有出色的穿透力。这些特性促使头孢曲松被应用于治疗细菌性腹膜炎,这是兽医医学中的一种腹部疾病,存在潜在死亡风险。测定血浆和腹膜液中的头孢曲松水平可用于评估不同给药情况下的药代动力学特征,并能观察是否达到所需浓度。因此,开发并验证了一种用于测定血浆和腹膜液中头孢曲松的方法,并将其应用于药代动力学特征研究。生物分析方法验证是根据广泛认可的实验进行的。使用两匹马作为该方法适用性的模型;将头孢曲松以单剂量腹腔内注射给这些动物。在经过充分验证的条件下,使用超高效液相色谱系统以反相色谱模式进行血浆和腹膜液分析。该方法在血浆中0.49至500μg/mL之间以及腹膜液中0.24至500μg/mL之间显示出线性关系。对这些基质中头孢曲松的定量分析有助于监测治疗情况。该方法在腹膜液中显示出更高的灵敏度和定量能力。

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