Cap-LC/MS法测定拉呋替丁血药浓度及其胶囊的人体相对生物利用度研究  

Determination of Lafutidine in human plasma and its capsules by Cap-LC/MS and pharmacokinetic study

作　　者：丁一冰[1] 樊夏雷[2] 沈建平[3] 

机构地区：[1]中国药科大学分析测试中心,南京210009 [2]江苏省药品检验所,南京21008 [3]南京医科大学临床药理研究所,南京210029

出　　处：《药物分析杂志》2006年第12期1757-1759,共3页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立人血浆中拉呋替丁的 Cap-LC/MS 定量方法,测定拉呋替丁胶囊和片剂的血药浓度及药动学参数,考察其生物等效性。方法:血浆样品中加入内标氯雷他定,经液液萃取、浓集后经毛细管柱色谱分离,流动相为乙肼-10 mmol·L^(-1)醋酸胺(pH 7.0)(78:22,V:V),经 ESI(+)源进入四级杆飞行时间串联质谱检测,提取拉呋替丁和内标的准分子离子(m/z)432.2和383.2。20名受试者单剂量(10 mg)双交叉口服受试胶囊与参比片。采用非房室模型法计算药动学参数。结果:血浆样品线性范围为5.004～834.0 ng·mL^(-1);提取回收率大于83.2%,准确度偏差小于±8.0%,日内和日间变异系数分别小于8.6%和17.4%。血浆样品-20℃放置20 d,RSD 小于10.1%。胶囊与参比片的药动学参数分别为:T_(1/2)3.51±0.49和3.44±0.53 h,T_(max)1.5±0.3和1.6±0.3 h,C_(max)177.3±23.0和177.5±26.1 ng·mL^(-1),AUC_(0-12)749.4±97.0和743.6±98.5ng·h·mL^(-1),AUC_(0-∞)817.1±1 10.3和808.5±111.7 ng·h·mL^(-1),胶囊的相对生物利用度为101.1±6.7%。两制剂的C_(max)、AUC_(0-12)、AUC_(0-∞)和 T_(max)经统计学检验均无显著性差异(P>0.05)。结论:本方法专属性强,灵敏度好,准确性高。受试胶囊与参比片生物等效。Objective： To establish a Cap - LC/MS method for determination of lafutidine in human plasma, and to study pharmacokinetics and bioavailability of its capsules. Methods： After adding internal standard, the plasma samples were extracted,and concentrated before being injected onto a capillary column. The mobile phase consisted of CH3CN - 10 mmolL^-1 NH4AC（ pH 7.0） （78：22 ,V： V）. ESI source was in positive ion mode. Tof MS was used for data acquisition. Masses（m/z） 432.2 and 383.2 were chosen for lafufidine and IS. Plasma concen - trations of 20 volunteers after a single dose（ 10 mg） of test capsules and reference tablets were determined at random by a 2 way crossover design. Results：The assay exhibited a linear range from 5.004 to 834.0 ng· mL^-1 of plasma concentration. Recovery of extraction was above 83.2%, and the inter - and intra - day coefficient was below 8.6% and 17. 4%. The accuracy bias was within 8.0%. The pharmacokinetic parameters of capsules and tablets were described as followed：T1/2 were 3.51 ±0.49 and 3.44 ±0.53 h,Tmax were 1.5 ±0.3 and 1.6 ±0.3 h,Cmax were 177.3 ±23.0 and 177.5 ±26.1 ng · mL^-1,AUC0-12were 749.4 ±97.0 and 743.6 ±98.5 ng · h · mL^-1, AUC0-∞ were 817. 1 ± 110.3 and 808.5 ± 111.7 ng · h · mL^- 1, respectively. The relative bioavailability was 101.1±6. 7%. Conclusions：The method was proved sensitive and efficient for pharmacokinetic study for lafutidine. The test capsules were of bioequivalence to the reference tablets.

关 键 词：拉呋替丁 高效毛细管液相质谱联用法 药代动力学 

分 类 号：R917[医药卫生—药物分析学]