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固相微萃取结合液相色谱-质谱法在人全血和组织样品中抗生素药物及其代谢物的测定中的应用。

Application of solid phase microextraction followed by liquid chromatography-mass spectrometry in the determination of antibiotic drugs and their metabolites in human whole blood and tissue samples.

机构信息

Department of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University, Gagarin 7, 87-100 Torun, Poland.

Department of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University, Gagarin 7, 87-100 Torun, Poland; Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Wilenska 4, 87-100 Torun, Poland.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jun 1;1086:153-165. doi: 10.1016/j.jchromb.2018.04.013. Epub 2018 Apr 12.

Abstract

A sensitive, rapid and specific analytical method using high performance liquid chromatography coupled with mass spectrometry (HPLC-QqQ-MS) was developed to determine selected antibiotic drugs and their metabolites (amoxicillin, cefotaxime, ciprofloxacin, clindamycin and metronidazole; amoxycilloic acid, 4-hydroxyphenyl glycyl amoxicillin, desacetyl cefotaxime, 3-desacetyl cefotaxime lactone, ciprofloxacin N-oxide, N-demethylclindamycin, clindamycin sulfoxide, and hydroxy metronidazole) in human whole blood and vascularized tissue after single oral administration. The samples were prepared by solid phase microextraction with C18 fibers (SPME) and determined on a GRACE analytical C18 column, Vision HT (50 × 2 mm, 1.5 μm) at the flow rate of 0.4 mL min using water and acetonitrile (containing 0.1% formic acid) as the mobile phase. The proposed method was successfully applied in a pharmacokinetic study of the selected antibiotic drugs and their metabolites in real human samples. Additionally, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI/TOF-MS) was used for identification and qualification analysis of the target compounds.

摘要

建立了一种灵敏、快速和专属性强的分析方法,采用高效液相色谱-串联质谱法(HPLC-QqQ-MS),用于测定人全血和血管化组织中单口服给药后选定的抗生素药物及其代谢物(阿莫西林、头孢噻肟、环丙沙星、克林霉素和甲硝唑;阿莫西林酸、4-羟基苯甘氨酰阿莫西林、头孢噻肟去乙酰基、3-去乙酰基头孢噻肟内酯、环丙沙星 N-氧化物、N-去甲基克林霉素、克林霉素亚砜和羟基甲硝唑)。样品采用 C18 纤维固相微萃取(SPME)进行预处理,在 GRACE 分析型 C18 柱(Vision HT,50×2mm,1.5μm)上,以水和乙腈(含 0.1%甲酸)为流动相,流速为 0.4mL/min 进行测定。该方法成功应用于选定的抗生素药物及其代谢物在真实人体样本中的药代动力学研究。此外,基质辅助激光解吸/电离飞行时间质谱(MALDI/TOF-MS)用于目标化合物的鉴定和确证分析。

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