LC-MS/MS法测定人血浆中重酒石酸长春瑞滨的浓度及其药动学研究  

Concentration Determination of Vinorelbine Bitartrate in Human Plasma by LC-MS/MS

作　　者：刘沛[1] 刘磊[1] 刘志浩[2] 王长远[2] 

机构地区：[1]大连市第三人民医院药剂科,辽宁大连116033 [2]大连医科大学药学院,辽宁大连116044

出　　处：《中国药房》2015年第20期2774-2777,共4页China Pharmacy

摘　　要：目的：建立测定人血浆中重酒石酸长春瑞滨浓度的方法,研究长春瑞滨在人体的药动学过程。方法：以固相萃取（SPE）技术处理样品后应用液相色谱-串联质谱（LC-MS/MS）法进样测定。色谱柱为Agilent Extend C18,流动相为5 mmol/L醋酸铵溶液（p H10.5）-乙腈-甲醇（18∶10∶72,V/V/V）,流速为0.4 ml/min;采用电喷雾离子源（ESI）,以多重反应监测（MRM）模式扫描,负离子方式检测。用于定量分析的离子反应分别为m/z 779.50→m/z 122.10（长春瑞滨）和m/z 811.60→m/z 224.50（内标,长春碱）。采用3p97程序计算药动学参数。结果：内源性杂质不干扰测定,无明显的基质效应;定量下限为2 ng/ml,长春瑞滨血药浓度在2.0~4 000.0 ng/ml范围内线性关系良好（r=0.997 8）;日内、日间精密度和准确度符合生物样本测定要求。30 mg/m2、40 mg/m2长春瑞滨注射用乳剂组及30 mg/m2长春瑞滨注射液组t1/2γ分别为（37.958±34.256）、（47.835±54.231）、（76.873±40.537）h,cmax分别为（1 426.250±397.562）、（1 700.125±624.669）、（2 187.500±828.040）ng/ml,AUC0-48 h分别为（75 839±19 551）、（82 088±14207）、（95 318±18 208）mg·h/L。结论：该试验建立的测定方法灵敏度好、准确度高、专属性强,适用于人体中长春瑞滨血药浓度的测定和药动学研究。长春瑞滨在肿瘤患者体内的代谢过程属于一级动力学三室模型。OBJECTIVE： To establish a method for determining the concentration of vinorelbine bitartrate in human plasma, and study the pharmacokinetic process of vinorelbine in human plasma. METHODS： The samples were extracted with Solid-phase extraction （SPE）. LC-MS/MS was performed on the column of Agilent Extend C18 with the mobile phase of 5 mmol/L ammonium ac- etate solution （pH10.5）-acetonitrile-methanol （18：10：72, V/V/V） at the flow rate of 0.4 ml/min, the ion source was ESI and MRM mode was used to scan positive ion detection. The ion reaction of quantitative analysis was m/z 779.50→m/z 122.10 （vinorelbine） and m/z 811.60→m/z 224.50 （internal standard, vinblastine）. 3p97 was used to calculate the pharmacokinetic parameters. RESULTS： The determination was not interfered by endogenous impurities, and there was no matrix effect; the lowest limit of quantita- tive analysis was 2.0 ng/ml with the linear range of 2.0-4 000.0 ng/ml （r=0.997 8） ; the linear range of vinorelbine in plasma was. The intra-day and inter-day precisions and accuracy results were all in line with the acceptable limit across all concentrations, t1/2r of 30 mg/m^2, 40 mg/m^2 Vinorelbine Emulsion for Injection groups and 30 mg/m^2 Vinorelbine for Injection group were （37.958 ± 34.256）, （47.835 ± 54.231 ）, （76.873 ± 40.537）h respectively, Cmax were（ 1 426.250 ± 397.562）, （1 700.125 ± 624.669）, （2 187.500 ± 828.040）ng/ml respectively,AUC0-48 h were（75 839 ± 19 551）,（82 088 ± 14 207）,（95 318 ± 18 208）mg.h/L respectively. CONCLU- SIONS： The method is rapid, sensitive and specific, and suitable for the determination of vinorelbine and pharmacokinetic study. Metabolic processes of vinorelbine can be described as first order process of three-compartment model in cancer patients.

关 键 词：长春瑞滨 液相色谱-串联质谱法 药动学 血药浓度 

分 类 号：R969.1[医药卫生—药理学] R979.1[医药卫生—药学]