LC-MS/MS法测定氨氯地平血药浓度及其片剂的生物等效性研究  

Determination of Amlodipine Concentration in Human Plasma by LC-MS/MS Method and Bioequivalence Study of Its Tablets

作　　者：张丽娜[1] 刘曼[1] 杨漫[1] 杜爱华[1] 张娅喃[1] 张丹[1] 韩静[1] 王晓琳[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：《中国药房》2013年第10期910-913,共4页China Pharmacy

摘　　要：目的:建立测定人血浆中氨氯地平血药浓度的方法,并评价2种苯磺酸氨氯地平片的生物等效性。方法:人血浆样本经液-液萃取后,选用ZorbaxSB-C18NarrowBore色谱柱,以甲醇-10mmol/L乙酸铵(90:10,V/V)为流动相,流速为0.3ml/min,选用API3200型三重四极杆串联质谱仪的多重反应监测(MRM)扫描方式进行监测,电喷雾电离(ESI)离子化源,正离子方式,选择监测离子反应分别为m/z409.2→m/z238.2(氨氯地平)和m/z256.2→m/z167.3(苯海拉明,内标)。24名健康受试者随机于2个周期交叉口服相同剂量的苯磺酸氨氯地平片受试制剂(国产)或参比制剂(进口),考察其生物等效性。结果:氨氯地平和苯海拉明的保留时间分别约为2.79、2.43min;氨氯地平的血药浓度在0.10～10.0ng/ml范围内线性关系良好(r=0.9997),定量下限为0.10ng/ml,日内、日间RSD均<15%,相对偏差(RE)均在±15%范围以内,平均提取回收率为(84.7±5.5)%,平均基质效应因子为(76.5±8.4)%。以AUC0-120h计,受试制剂相对于参比制剂的生物利用度为(105.8±20.9)%。结论:该方法快速、灵敏、专属性强、重现性好,适用于人血浆中氨氯地平的测定,可用于苯磺酸氨氯地平片的人体生物等效性研究;2种制剂生物等效。OBJECTIVE： To develop method for the determination of amlodipine in human plasma, and to evaluate bioequivalence of 2 kinds of Amlodipine besylate tables in healthy volunteers. METHODS ： After liquid-liquid extraction, the samples were separated on Zorbax SB-C18 Narrow Bore column with mobile phase consisted of methanol-10 mmol/L ammonium acetate （90：10, V/V） at the flow rate of 0.3 ml/min. Detection was carried out by electrospray positive ionization mass spectrometry in type API3200 multiple reaction monitoring （MRM） mode. The MRM transitions of m/z 409.2→m/z 238.2 and m/z 256.2→m/z 167.3 were used to quantify amlodipine and diphenhydramine （I.S.）, respectively. The bioequivalence of test preparation and reference preparation of Amlodipine besylate tablets in 24 healthy volunteers after oral administration were investigated in a randomized, two-periods cross-over study. RESULTS： Amlodipine and I.S. were eluted at 2.79 min and 2.43 rain, respectively. The linear range of amlodipine were 0.10-10.0 ng/ml （r=0.999 7） with the lowest quantitation limit of 0.10 ng/ml. Intra-day and inter-day RSDs were both less than 15%; relative errors （RE） were within ± 15%. The mean extraction recovery was （84.7 ± 5.5）%, and the mean matrix effect factor was （76.5 ± 8.4）%. The relative bioavailability of test preparation to reference preparation was （105.8 ± 20.9）% according to AUC0-120 h. CONCLUSIONS： The method is rapid, sensitive, selective and reproducible, and it is suitable for the determination of amlodipine in human plasma and bioequivalence study of Amlodipine besylate tablets in healthy volunteers.Two preparations are bioequivalent.

关 键 词：氨氯地平 高效液相色谱串联质谱法 生物等效性 

分 类 号：R969.1[医药卫生—药理学] R972[医药卫生—药学]