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采用在线微透析和微径液相色谱法测定大鼠血液中游离头孢菌素的含量及其药代动力学分析

Measurement and pharmacokinetic analysis of unbound cephaloridine in rat blood by on-line microdialysis and microbore liquid chromatography.

作者信息

Tsai T H, Kao H Y, Chen C F

机构信息

National Research Institute of Chinese Medicine, 155-1 Li-Nong Street Section 2, Taipei 112, Taiwan.

出版信息

Biomed Chromatogr. 2001 Apr;15(2):79-82. doi: 10.1002/bmc.40.

DOI:10.1002/bmc.40
PMID:11268046
Abstract

A technique involving rapid sampling of cephaloridine in rat blood was achieved using a combination of microdialysis and sensitive microbore liquid chromatography. A microdialysis probe was inserted into the jugular vein/right atrium of a Sprague-Dawley rat. Then after a real-time collection of the analyte by microdialysis, the dialysate was automatically injected into a liquid chromatographic system via an on-line injector. Following a 2 h stabilization period after the surgical procedure, cephaloridine (20 mg/kg, i.v.) was then administered via the femoral vein. Isocratic elution of cephaloridine was carried out with a mobile phase containing methanol-20 mM monosodium phosphate (25:75, v/v, pH 5.5), and the flow rate of the mobile phase was 0.05 mL/min within 10 min. Intra- and inter-assay accuracy and precision of the assay were each less than 10%. The in vivo recovery of the cephaloridine from the microdialysate was 49.7 +/- 8.0% and 42.4 +/- 8.4% for 0.5 and 1 microg/mL standards (n = 6), respectively. Based on the pharmacokinetic analysis, the elimination half-life was 32.2 +/- 8.6 min by cephaloridine administration (20 mg/kg, i.v., n = 6).

摘要

采用微透析和灵敏的微径液相色谱联用技术,实现了大鼠血液中头孢菌素的快速采样。将微透析探针插入Sprague-Dawley大鼠的颈静脉/右心房。然后通过微透析实时收集分析物后,透析液通过在线进样器自动注入液相色谱系统。手术操作后经过2小时的稳定期,随后经股静脉给予头孢菌素(20mg/kg,静脉注射)。用含有甲醇-20mM磷酸二氢钠(25:75,v/v,pH 5.5)的流动相进行头孢菌素的等度洗脱,流动相流速在10分钟内为0.05mL/min。该测定的批内和批间准确度和精密度均小于10%。对于0.5和1μg/mL的标准品(n = 6),从微透析液中头孢菌素的体内回收率分别为49.7±8.0%和42.4±8.4%。基于药代动力学分析,给予头孢菌素(20mg/kg,静脉注射,n = 6)后的消除半衰期为32.2±8.6分钟。

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