LC-MS/MS法测定人血浆中替加环素的浓度及其临床应用
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篇名: LC-MS/MS法测定人血浆中替加环素的浓度及其临床应用
TITLE:
摘要: 目的:建立测定人血浆中替加环素(TGC)浓度的方法。方法:血浆样品经乙腈沉淀后,采用液相色谱-串联质谱(LC-MS/MS)法测定,以d9-TGC为内标,色谱柱为Kromasil C18,流动相为水(含0.05%三氟乙酸)-乙腈,梯度洗脱,流速为0.6 ml/min,柱温为40 ℃,采用电喷雾离子源,以多反应监测方式进行正离子扫描,用于定量分析的离子对分别为m/z 586.3→513.2(TGC)、m/z 595.3→514.3(内标)。结果:TGC血药浓度在25~2 000 ng/ml范围内线性关系良好(r=0.999 8),定量下限为25 ng/ml;日内、日间RSD为3.15%~7.23%,相对偏差(RE)为-4.53%~10.48%;血浆样品在经历3次冻融循环、室温和自动进样器中各放置24 h、冷冻放置42 d等条件下均稳定,RSD<15%。临床检测1例泛耐药菌感染患者体内TGC血药浓度为0~438.0 ng/ml(给药后0~12 h)。结论:该方法准确、灵敏、专属性强,可用于临床TGC血药浓度监测及药动学研究。
ABSTRACT: OBJECTIVE: To establish the method for the determination of tigecycline (TGC) in human plasma. METHODS: After precipitated by acetonitrile, the plasma sample was determined by LC-MS/MS. Using d9-TGC as internal standard, Kromasil C18 column was used with mobile phase consisted of water (containing 0.05% TFA)-acetonitrile (gradient elution) at flow rate of 0.6 ml/min, column temperature of 40 ℃. The ion transitions were performed under ESI positive MRM model at m/z 586.3→513.2 and m/z 595.3→514.3 for TGC and internal standard, respectively. RESULTS: The linear range of TGC was 25-2 000 ng/ml (r=0.999 8), and lowest quantification limit was 25 ng/ml; intra-day and inter-day RSD was 3.15%-7.23%, and relative error was     -4.53%-10.48%. Plasma sample kept stable after 3 times of freezing and thawing cycle, at room temperature for 24 h, in automatic sample injector for 24 h and freezing for 42 d (RSD<15%). Plasma concentration of TGC was 0-438.0 ng/ml in one patient with pan-drug resistant bacteria infection(0-12 h after administration). CONCLUSIONS: The developed method is accurate, sensitive and specific, and can be used for plasma concentration determination of TGC and pharmacokinetic study.
期刊: 2016年第27卷第5期
作者: 梅升辉,罗旭颖,李倩,杨莉,赵志刚,朱乐亭 ,石广志
AUTHORS: MEI Shenghui,LUO Xuying,LI Qian,YANG Li,ZHAO Zhigang,ZHU Leting,SHI Guangzhi
关键字: 液相色谱-串联质谱法;替加环素;血药浓度;临床应用
KEYWORDS: LC-MS/MS; Tigecycline; Plasma concentration; Clinical application
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