高效液相色谱-串联质谱测定人血浆中烯丙雌醇  

Determination of allylestrenol in human plasma by liquid chromatography-tandem mass spectrometry

作　　者：吴寅[1] 杭太俊[2] 徐晓峰[2] 陈晓莉[1] 赵培西[1] 金鑫[1] 王靖雯[1] 文爱东[1] 

机构地区：[1]第四军医大学西京医院药剂科,西安710032 [2]中国药科大学药物分析教研室,南京210009

出　　处：《中国新药杂志》2009年第12期1121-1124,共4页Chinese Journal of New Drugs

摘　　要：目的：建立人血浆中烯丙雌醇的LC-MS/MS浓度测定方法，并评价国产与进口烯丙雌醇片的人体生物等效性。方法：采用Curosil-PFP色谱柱（250 mm×4.6 mm，5μm）；柱温25℃；流动相为甲醇-水（95∶5）；流速为1.0 mL·min^-1；通过液相串联质谱，大气压化学电离（APCI），以选择反应监测（SRM）方式进行检测。结果：血浆中烯丙雌醇的最低定量限为0.04 ng·mL^-1，在0.04-20.0 ng·mL^-1范围内线性关系良好，批内及批间精密度RSD分别小于1.3%和3.1%。受试制剂与参比制剂的各主要药动学参数：Tmax分别为（1.9±0.5）和（2.0±0.7）h，Cmax分别为（13.63±4.05）和（13.00±3.77）ng·mL^-1，t1/2分别为（9.46±2.88）和（8.77±3.53）h，用梯形法计算AUC0-36 h分别为（46.88±17.48）和（45.16±16.81）ng·h·mL^-1。2种制剂的主要药动学参数Cmax和AUC0-36 h经对数转换后进行方差分析及双单侧t检验，并计算90%置信区间，表明2种制剂生物等效，相对生物利用度为（106.4±29.1）%。结论：该方法简便、灵敏度高，2种烯丙雌醇制剂在人体内生物等效。Objective： To establish a LC-MS/MS method for the determination of allylestrenol in human plasma and to evaluate the bioequivalence of domestic and imported allylestrenol tablets in healthy volunteers. Methods：The samples were separated on a Curosil-PFP （250 mm × 4.6 mm,5 μm） chromatographic column at 25 ℃. The mobile phase consisted of methanol-water （95：5 ） at the flow-rate of 1.0 mL·min^-1 A Finnigan TSQ tandem mass equipped with atmospheric pressure chemical ionization source （APCI） was used as detector and operated in the positive ion mode and selected reaction monitoring （ SRM）. Results ：The low determination limit of allylestrenol in plasma was 0.04 ng·mL^-1 and a good linearity was obtained over a range of 0.04 -20.0 ng·mL^-1 The intra- and inter-run standard deviations were less than 1.3% and 3.1% , respectively. The pharmacokinetie parameters of the test and reference preparations were as follows ： Tmax （ 1.9 ± 0.5 ） and （2.0 ± 0.7 ） h, Cmax （ 13.63 ± 4.05） and （13.00±3.77） ng·mL^-1,t1/2（9.46±2.88） and （8.77 ±3.53） h,and AUC0-36h（46.88 ±17.48） and （45.16 ± 16.81 ） ng·h·mL^-1 , respectively. The relative bioavailability of the test product to the reference was （106.4 ± 29.1 ）%. Conclusion：This method is simple,sensitive and suitable for clinical pharmacokinetics or bioequivalence studies. The two allylestrenol formulations were bioequivalent.

关 键 词：烯丙雌醇 高效液相色谱-串连质谱 药动学 生物等效性 

分 类 号：R969.1[医药卫生—药理学]