UPLC-MS/MS法同时测定人血浆中卡马西平、文拉法辛、罗格列酮和硝苯地平的浓度  

Simultaneous Determination of Carbamazepine, Venlafaxine, Rosiglitazone and Nifedipine in Human Plasma by UPLC-MS/MS

作　　者：王伟[1] 丁仁奎[1] 李清艳[1] 祁妍敏[1] 

机构地区：[1]中国民用航空局民用航空医学中心/民航总医院航空医学研究所,北京100123

出　　处：《中国药房》2018年第2期194-198,共5页China Pharmacy

基　　金：中国民用航空总局科技项目(No.MHRD201042);中国民用航空局民航安全能力建设资金项目(No.DFS20160604)

摘　　要：目的:建立同时测定人血浆中卡马西平、文拉法辛、罗格列酮和硝苯地平浓度的方法。方法:血浆样品经甲醇(含0.1%甲酸)沉淀蛋白后,以盐酸吡格列酮为内标,采用超高效液相色谱-串联质谱法测定。色谱柱为Waters ACQUITY UPLC HSS C_(18),流动相为含0.01%甲酸的水溶液-含0.01%甲酸的甲醇溶液(梯度洗脱),流速为0.3 mL/min,柱温为50℃,进样量为5μL;采用电喷雾离子源,以多反应监测模式进行正离子扫描,用于定量分析的离子对分别为m/z 237.00→194.05(卡马西平)、m/z 278.20→58.10(文拉法辛)、m/z 358.08→135.04(罗格列酮)、m/z 347.15→315.17(硝苯地平)、m/z 357.09→134.06(内标)。结果:卡马西平、盐酸文拉法辛、盐酸罗格列酮、硝苯地平血药浓度的线性范围分别为2.00~2 000.00、2.12~2 120.00、2.00~2 000.00、2.04~1 020.00 ng/mL(r分别为0.995 9、0.990 5、0.991 5、0.991 0,n=5),最低检测限分别为0.200、0.106、0.100、1.020 ng/mL;日内、日间RSD均小于15%,相对误差的绝对值小于15%;提取回收率为65.66%~96.36%(RSD<15%,n=5),基质效应为80.99%~114.33%。采用该法测得2例癫痫患者体内卡马西平的血药浓度分别为(1 500.41±169.11)、(1 159.01±59.24)ng/mL(RSD分别为11.27%、5.60%,n=3),2例高血压患者体内硝苯地平的血药浓度分别为(14.68±1.92)、(21.18±3.59)ng/mL(RSD分别为16.98%、13.10%,n=3)。结论:该方法操作简便,专属性强,灵敏度、准确度高,可用于上述药物的血药浓度监测及药动学研究。OBJECTIVE： To develop a method for simultaneous determination of carbamazepine, venlafaxine, rosiglitazone and nifedipine in human plasma. METHODS： UPLC-MS/MS method was adopted to determine plasma sample after precipitated with methanol （containing 0.1% formic acid） using pioglitazone hydrochloride as internal standard. The determination was performed on Waters ACQUITY UPLC HSS C,8 column with mobile phase consisted of aqueous solution containing 0.01% formic acid-methanol containing 0.01% formic acid （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was 50 ℃, and sample size was 5 μL. ESI was used for positive ion scanning by multi reaction monitoring mode. The ion pairs for quantitative analysis were m/z 237.00 to 194.05 （earbamazepine）, m/z 278.20 to 58.10 （venlafaxine）, m/z 358.08 to 135.04 （rosiglitazone）, m/z 347.15 to 315.17 （nifedipine）, m/z 357.09 to 134.06 （internal standard）. RESULTS： The liner ranges of carbamazepine, venlafaxine hydrochloride, rosiglitazone hydrochloride and nifedipine were 2.00-2 000.00 （r=0.995 9, n=5）, 2.12-2 120.00（r=0.990 5, n=5）, 2.00-2 000.00（r=0.991 5, n=5） and 2.04-1 020.00（r=0.991 0,n=5） ng/mL; the minimum detection limits were 0.200, 0.106, 0.100, 1.020 ng/mL, respectively. RSDs of inter-day and intra-day were less than 15%. The absolute values of RE were less than 15%. The exlraction recoveries were 65.66%-96.36% （RSD% 〈15% ,n=5）, and matrix effects ranged 80.99%-114.33%. The plasma concentrations of carbamazepine in 2 epileptic patients were （1 500.41 ± 169.11）, （1 159.01 ± 59.24） ng/mL（RSD were 11.27%, 5.60%, n=3）. The plasma concentrations of nifedipine in 2 hypertensive patients were （14.68 ±1.92）, （21.18 ± 3.59）ng/mL（RSD were 16.98%, 13.10%, n= 3）. CONCLUSIONS. The method is simple, specific, sensitive, accurate and suitable for the monitoring of plasma concentration and pharmacodynamic study of above drugs.

关 键 词：卡马西平 文拉法辛 罗格列酮 硝苯地平 血药浓度 超高效液相色谱-串联质谱法 

分 类 号：R969.1[医药卫生—药理学] R917[医药卫生—药学]