高效液相色谱-质谱联用法测定人血浆中拉米夫定  

Determination of lamivudine in human plasma by LC-MS

作　　者：王洋[1] 刘文涛[1] 张弘[1] 毕开顺[1] 陈晓辉[1] 

机构地区：[1]沈阳药科大学药分教研室,辽宁沈阳110016

出　　处：《中国医院药学杂志》2010年第19期1654-1657,共4页Chinese Journal of Hospital Pharmacy

摘　　要：目的:建立高效液相色谱-质谱联用法测定人血浆中拉米夫定的浓度,并研究拉米夫定胶囊在健康人体的药动学。方法:血浆样品以法莫替丁作为内标,经1mol·L-1碳酸钠溶液碱化,异丙醇-醋酸乙酯(20∶80)萃取,以LC-MS法进行分析。色谱条件为Kromasil C18柱(150mm×4.6mm,5μm),甲醇-甲酸水(0.2%)为流动相,进行梯度洗脱。以电喷雾离子源(ESI源),正离子方式检测:扫描方式为选择离子监测(SIM),用于定量分析的离子分别为m/z230.05(拉米夫定)和m/z338.05(法莫替丁)。结果:测定血浆中拉米夫定在10～2500μg·L-1范围内线性关系良好,定量下限(LLOQ)为10μg·L-1,日内、日间精密度(RSD)均小于10.0%,拉米夫定提取回收率在73.8%～84.4%,RSD均小于10.0%。结论:该方法灵敏度高、专属性强,适用于人血浆中拉米夫定浓度的测定。OBJECTIVE To develop a I.C-MS method for the determination of lamivudine concentration in human plasma and study the pharmacokinetics in healthy volunteers after a single oral dose of 100 mg lamivudine capsule preparation. METHODS After adding famotidine as the internal standard and 1 mol·L ^-1 NaCO3 as the basification reagent,lamivudine was extracted from plasma by isopropyl alcoholethyl acetate（20：8（1, v/v）and the separation was carried on a Kromasil C18 column（ 150mm × 4. 6 mm, 5 μm）, mobile phase was consisted of methanolformic acid water（0. 2 %） with step-gradient elution, the flow rate was 0. 8 mL· min^-1. Lamivudine was determined by I.CMS in selected ion monitoring（SIM） mode, the ion combination of m/z 230. （75 and m/z 338. 05 were used for determination of lamivudine and the internal standard, respectively. RESULTS The cali- bration curve was in good linearity over the range of 0. 00-2 500 μg·L^-1. The lower limit of quantification（LLOQ） for lamivu- dine in plasma was 10μg·L^-1. Both of the intra-day and inter-day precision （RSD） were lower than 10. 0%. The recovery for lamivudine was between 73.8%-84. 4%, RSD was lower than 10. 0%. CONCLUSION The method used shown to be sensitive and specific for the determination of lamivudine in human plasma.

关 键 词：拉米夫定 高效液相色谱-质谱联用法 药动学 血药浓度 

分 类 号：R285.5[医药卫生—中药学]