作者：胡岚岚, 张乐, 汤建林

作者单位：陆军军医大学第二附属医院国家药物临床试验机构，重庆 400037

关键词：克拉霉素;固相萃取;UPLC-MS/MS;药代动力学;血浆

摘要：

建立专属的固相萃取（SPE）结合超高效液相色谱-串联质谱（UPLC-MS/MS）的分析方法，来测定人血浆中克拉霉素的浓度。以罗红霉素为内标，采用固相萃取法提取血浆，取上清液5 μL进样。色谱柱：Acquity UPLC BEH C18（2.1 mm×50 mm，1.7 μm），流动相：乙腈和0.1%甲酸水溶液，等度洗脱，流量为0.3 mL/min，分析时间2 min。正离子检测模式。结果表明：克拉霉素在0.05~6.40 μg/mL的浓度范围内呈线性，日内、日间精密度分别小于2.96%和5.22%，基质效应影响较小，相对回收率在88.33%~96.04%之间。口服克拉霉素胶囊剂后达峰浓度和达峰时间分别为2.17 μg/mL 和2.10 h。该方法可用于微量血浆测定，并可应用于成人或儿童感染后给予克拉霉素对其血药浓度的研究。

Quantification of clarithromycin in human plasma by UPLC-MS/MS with solid-phase extraction and its pharmacokinetic study
HU Lanlan, ZHANG Le, TANG Jianlin
National Drug Clinical Trial Institution, The Second Affiliated Hospital, Army Medical University, Chongqing 400037, China
Abstract: A specific method using UPLC-MS/MS with solid-phase extraction (SPE) was developed for the determination of clarithromycin in plasma. The human plasma was extracted with a solid-phase extraction which contained roxithromycin as an internal standard. After centrifugation, 5 μL of supernatant was injected onto the UPLC-system. Compounds were separated on a Acquity UPLC BEH C18 (2.1 mm×50 mm, 1.7 μm) column using gradient elution with mobile phase acetonitrile (mobile phase A) and 0.1% formic acid (mobile phase B) with a flow rate of 0.3 mL·min^–1 and a total runtime of 2.0 min. Clarithromycin and the internal standard were detected using positive ion electrospray ionization followed by tandem mass spectrometry (ESI-MS/MS). The assay allowed quantification of clarithromycin plasma concentrations in the range from 0.05-6.40 μg/mL. Inter-assay inaccuracy was within 2.96% and inter-assay precision was less than 5.22%. Matrix effects were minor, the recovery of clarithromycin was between 88.33% and 96.04%. The maximum concentration (C_max) and the time to reach this concentration (T_max) were 2.17 μg/mL and 2.10 h, respectively. The developed method required less plasma sample volume. The method was applied in a clinical pharmacokinetic study in which adult/children received clarithromycin for the treatment of infection.
Keywords: clarithromycin;SPE;UPLC-MS/MS;pharmacokinetics;plasma
2020, 46(10):43-47,53  收稿日期: 2020-07-14;收到修改稿日期: 2020-08-10
基金项目:
作者简介: 胡岚岚(1984-),女,安徽岳西县人,主管药师,硕士,研究方向为药物分析学
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