药学学报, 2019, 54(4): 695-700
引用本文:
刘珊珊, 耿雅杰, 夏媛媛, 刘静媛, 魏广力, 司端运. LC-MS/MS法定量测定人血浆中诺氟沙星浓度的分析方法研究及其应用[J]. 药学学报, 2019, 54(4): 695-700.
LIU Shan-shan, GENG Ya-jie, XIA Yuan-yuan, LIU Jing-yuan, WEI Guan-li, SI Duan-yun. Quantification of norfloxacin in human plasma by LC-MS/MS and validation of the analytical method[J]. Acta Pharmaceutica Sinica, 2019, 54(4): 695-700.

LC-MS/MS法定量测定人血浆中诺氟沙星浓度的分析方法研究及其应用
刘珊珊1,2, 耿雅杰2, 夏媛媛2, 刘静媛2, 魏广力2, 司端运2
1. 天津医科大学研究生院, 天津 300070;
2. 天津药物研究院释药技术与药代动力学国家重点实验室, 天津 300193
摘要:
建立快速、灵敏的LC-MS/MS法测定人血浆中诺氟沙星的浓度,并将该方法应用于诺氟沙星在人体内的药代动力学研究。以环丙沙星为内标,血浆样品经甲醇沉淀后,通过Symmetry®C18色谱柱(100 mm×4.6 mm,5 μm)进行分离,使用甲醇溶液(含0.3%甲酸)-水溶液(含0.3%甲酸和5%甲醇)作为流动相,进行梯度洗脱,流速为0.45 mL·min-1。通过电喷雾电离源(ESI),以多反应监测(MRM)模式进行正离子检测,诺氟沙星、环丙沙星的MRM离子对分别为m/z 320.3→302.1、m/z 332.3→314.1。人血浆中诺氟沙星在10~1 000 ng·mL-1浓度内线性关系良好(r2>0.99),定量下限为10 ng·mL-1;定量下限和质控样品的批内、批间精密度(RSD%)在2.64%~7.23%之间,准确度(RE%)在±5.00%以内。健康人口服诺氟沙星片100 mg后主要药代动力学参数tmaxCmax、AUC0-tt1/2分别为:1.28±0.364 h、627±171 ng·mL-1、2 938 ±850 h·ng·mL-1、6.01±1.36 h。本研究建立的LC-MS/MS分析方法灵敏度高且样品处理方法简单快速,满足生物分析的法规要求,经柳州市工人医院医学伦理委员会的批准,可应用于人体内诺氟沙星的药代动力学研究。
关键词:    诺氟沙星      LC-MS/MS      药代动力学     
Quantification of norfloxacin in human plasma by LC-MS/MS and validation of the analytical method
LIU Shan-shan1,2, GENG Ya-jie2, XIA Yuan-yuan2, LIU Jing-yuan2, WEI Guan-li2, SI Duan-yun2
1. Tianjin Medical University Graduate School, Tianjin 300070, China;
2. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China
Abstract:
A LC-MS/MS method for quantification of norfloxacin in human plasma had been developed. This method was applied to the pharmacokinetics study of norfloxacin in the human. The plasma sample was precipitated by methanol and ciprofloxacin was used as the internal standard (IS). Chromatographic separation was performed on a Symmetry® C18 column(100 mm×4.6 mm, 5 μm). Mobile phase contains 0.3% formic acid and 5% methanol in deionized water at a flow rate of 0.45 mL·min-1. Norfloxacin and ciprofloxacin (IS) were ionized with an ESI source and operated in positive ion mode. The detected ions were m/z 320.3→302.1 (norfloxacin), m/z 332.3→314.1 (ciprofloxacin). This LC-MS/MS method yielded a linearity over the range of 10-1 000 ng·mL-1 with the lower limit of quantitation (LLOQ) of 10 ng·mL-1. The intra and inter-assay precisions (RSD%) were within the range of 2.64%-7.23% and the accuracy (RE%) was less than ±5.00%. The pharmacokinetic parameters tmax, Cmax, AUC0-t, and t1/2 were 1.28±0.364 h, 627±171 ng·mL-1, 2 938±850 h·ng·mL-1, and 6.01±1.36 h, respectively. This LC-MS/MS method was proven simple, sensitive, rapid and suitable for pharmacokinetics study of norfloxacin in the human and Approved by the Medical Ethics Committee of Liuzhou Workers' Hospital.
Key words:    norfloxacin    LC-MS/MS    pharmacokinetics   
收稿日期: 2018-10-10
DOI: 10.16438/j.0513-4870.2018-0913
基金项目: 国家自然科学基金青年科学基金资助项目(81503154).
通讯作者: 司端运
Email: sidy@tjpr.com
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