UPLC-MS/MS法测定人血浆中罗匹尼罗的浓度及其药动学研究  

Determination of Ropinirole in Human Plasma by UPLC-MS/MS and Its Pharmacokinetic Study

作　　者：黄晨蓉 许青青[2] 缪丽燕[1] 

机构地区：[1]苏州大学附属第一医院临床药理室,江苏苏州215006 [2]苏州大学药学院,江苏苏州215000

出　　处：《中国药房》2017年第2期177-181,共5页China Pharmacy

基　　金：国家自然科学基金青年科学基金项目(No.81503159)

摘　　要：目的:建立测定人血浆中罗匹尼罗浓度的方法,并用于药动学研究。方法:血浆样品经乙腈沉淀后,以阿替洛尔为内标,采用超高效液相色谱-串联质谱法测定。色谱柱为Waters ACQUITY UPLC BEH Amide,流动相为水(含10 mmol/L乙酸铵和0.1%甲酸)-乙腈(85∶15,V/V),流速为0.3 m L/min,柱温为40℃,进样量为5μL。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 261.2→114.1(罗匹尼罗)和m/z 267.2→145.0(内标)。选择8例健康受试者,男、女各半,单次给予盐酸罗匹尼罗片1.0 mg后,采用该法测定给药前后罗匹尼罗的血药浓度,采用Win Nonlin 6.3软件计算其药动学参数。结果:罗匹尼罗血药浓度在0.02~2 ng/m L范围内线性关系良好(r=0.997 3),批内、批间RSD<10%,准确度为95.2%~99.7%,提取回收率为68.5%~79.9%,基质效应和稀释效应均不影响其血药浓度的测定。8例健康受试者口服盐酸罗匹尼罗片1.0 mg后,c_(max)为(2.1±0.5)ng/m L,t_(max)为(1.0±0.5)h,t1/2为(4.7±1.5)h,AUC_(0-36 h)为(14.7±6.0)ng·h/m L,AUC_(0-∞)为(15.1±6.1)ng·h/m L;不同性别受试者主要药动学参数比较,差异均无统计学意义(P>0.05)。结论:该方法操作简便、灵敏度高、分析时间短,适用于人血浆中罗匹尼罗的浓度测定及药动学研究。OBJECTIVE ： To develop a method for the determination of ropinirole in human plasma and pharmacokinetic study. METHODS： After precipitated with acetonitrile, using atenolol as internal standard, plasma sample was determined by UPLC-MS/ MS. The separation was performed on Waters ACQUITY UPLC BEH Amide column with mobile phase consisted of water （containing 10 mmol/L ammonium acetate and 0.1% formic acid）-acetonitrile （85： 15, V/V） at flow rate of 0.3 mL/min. The column temperamre was set at 40 ℃, and sample size was 5 μL. The analyses were carried out by ESI under MRM model in positive mode. The mass transition ion-pairs were as follows： m/z 261.2→114.1 （ropinirole） and m/z 267.2→145.0 （internal standard）. 8 healthy volunteers were selected with a gender ratio of half to half, and were given Ropinirole hydrochloride tablets 1.0 mg. Plasma concentrations of ropinirole were determined before and after medication. The pharmacokinetic parameters were calculated by WinNonlin 6.3 software. RESULTS： The linear range of ropinirole were 0.02-2 ng/mL （r=0.997 3） with RSDs of inter-batch and intra-batch〈10% ; accuracy ranged 95.2%-99.7%, and extraction recoveries ranged 68.5%-79.9%. Both matrix effects and dilution effects didn＇t influ- ence the determination of plasma concentration. The main pharmacokinetic parameters of ropinirole in 8 healthy volunteers after oral administration of Ropinirole hyolrocholride tablets 1.0 mg were as follows： cmax was （2.1 ± 0.5） ng/mL, tmax was （1.0 ± 0.5） h, t1/2 was （4.7± 1.5） h, AUC0-36h was （14.7±6.0）ng·h/mL, AUC0-∞ was （15.1 ± 6.1）ng·h/mL. There was no statistical significance in main pharmacokinetic parameters between different gender （P〉0.05）. CONCLUSIONS： The method is simple, sensitive and less time-constuning. It is suitable for the plasma concentration determination and pharmacokinetic study of ropinirole in human.

关 键 词：超高效液相色谱-串联质谱法 罗匹尼罗 血药浓度 药动学 

分 类 号：R945[医药卫生—微生物与生化药学]