重酒石酸卡巴拉汀国产片剂与进口胶囊的生物等效性研究  

Bioequivalence evaluation of domestic tablets and imported capsules of rivastigmine tartrate

作　　者：王晓琳[1] 张丽娜[1] 杜爱华[1] 张娅喃[1] 张丹[1] 刘曼[1] 杨漫[1] 刘会臣[1] 

机构地区：[1]航天中心医院临床药理室,北京100049

出　　处：《药物分析杂志》2013年第9期1496-1500,共5页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:研究重酒石酸卡巴拉汀在中国健康受试者体内的药代动力学,并评价其国产片剂(受试制剂)与进口胶囊(参比制剂)的生物等效性。方法:采用LC-MS/MS法测定20名健康受试者口服卡巴拉汀制剂后血浆中的卡巴拉汀浓度。采用DAS 2.1.1软件计算主要药动学参数,并评价其生物等效性。色谱条件:采用Agilent ZORBAX SB-C18色谱柱(150 mm×2.1mm,5μm),以甲醇-10 mmol·L-1醋酸铵(含0.1%甲酸)(50∶50)为流动相,流速0.3 mL·min-1,柱温35℃;质谱条件:采用离子喷雾离子化源,正离子方式检测,多重反应监测(MRM),用于定量分析的离子反应分别为m/z 251.2→206.3(卡巴拉汀)和m/z 275.2→230.2(氯苯那敏)。结果:受试制剂与参比制剂的AUC0-t分别为(14.36±9.61)和(13.56±8.88)ng·h·mL-1;C max分别为(8.03±4.01)和(7.60±3.37)ng·mL-1;T max分别为(0.75±0.31)和(0.70±0.26)h;t1/2分别为(1.12±0.24)和(1.13±0.24)h。以卡巴拉汀计,受试制剂的相对生物利用度为(107.0±16.2)%。结论:试验结果表明受试制剂和参比制剂口服后吸收速度和程度相当,具有生物等效性。Objective： To investigate the pharmacokinetics of rivastigmine tartrate in healthy Chinese volunteers, and evaluate the bioequivalence between its domestic tablet（test formulation） and imported capsule（ reference for- mulation）. Methods ： The plasma concentrations of rivastigmine were determined using LC - MS/MS method in 20 healthy Chinese volunteers after oral administration of rivastigmine formulation. The main pharmaeokinetic parame- ters of rivastigmine and bioequivalence between the two formulations were calculated by DAS 2. 1.1. The separation was achieved on an Agilent ZORBAX SB -C18 column（150 mm ×2. 1 mm,5μm） , the mobile phase consisted of methanol - 10 mmol. L-1 ammonium acetate containing 0. 1% formic acid（50： 50） at a flow rate of 0. 3 mL . min-1 , and the column temperature was 35 ℃. ESI source was applied and operated in positive ion mode and mul- tiple reaction monitoring（MRM）. The ion combination of m/z 251.2→206.3 and m/z 275.2→230. 2 was used to qualify rivastigmine and chlorpheniramine respectively. Results： The AUC0-t was （14. 36 ：± 9.61 ） and （13.56 ± 8.88） ng. h-mL-1, Cmax was （8.03 ±4.01） and （7.60 ±3.37） ng. mL-1 , TmaxWaS （0.75 ±0.31） and （0. 70 ±0. 26） h, and t1/2 was （1.12 ±0.24） and （1.13 ±0. 24） h for the test and reference formulations, re- spectively. The relative bioavailability of the test formulation was （107.0± 16.2）%. Conclusion： The results demonstrate that the test and reference formulations are bioequivalent, and there is no significant difference in the rate or extent of absorption after oral administration.

关 键 词：重酒石酸卡巴拉汀 血药浓度 人血浆样品 药代动力学 生物等效性 液相色谱一串联质谱法 

分 类 号：R917[医药卫生—药物分析学]