大鼠血浆中抗抑郁新药阿姆西汀浓度检测方法的建立及其药代动力学

Establishment of a concentration test method of S-071031B in rat plasma and its pharmacokinetics

目的：应用液相色谱-串联质谱法（LC-MS/MS）建立大鼠血浆中阿姆西汀（S-071031B）浓度测定方法，并考察大鼠灌胃给予阿姆西汀后的药代动力学。方法采用LC-MS/MS方法，以盐酸苯环壬酯左旋体（ L-8021）为内标，C18柱为分析柱，流动相为含0．1％甲酸的水-乙腈体系，流速为0．3 ml/min，采用电喷雾正离子（ESI ＋）、选择反应监测（SRM）模式进行检测。绘制血药浓度-时间曲线并利用DAS 2．0计算药代动力学参数。结果大鼠血浆中内源性杂质不干扰阿姆西汀和内标的测定，阿姆西汀的线性范围为2～1000 ng/ml （r2＝0．9965），定量限为2 ng/ml，日内、日间精密度和准确度，绝对回收率和基质效应均符合生物样品测定需要。大鼠口服灌胃后在（0．8±0．3）h达到（287．2±50．8）μg/L的峰值浓度，t1/2为（2．9±0．6）h，AUC（0-∞）为（1372．6±255．3）μg/L· h。结论本方法灵敏度高、特异性好，可用于血浆中阿姆西汀的浓度测定及其药代动力学研究。

Objective To establish an LC-MS/MS method for determination of S-071031 B, a novel antidepressant , in rat plasma and to study its pharmacokinetic profiles .Methods An LC-MS/MS method was established to determine S-071031B in rat plasma, and L-8021 was employed as the internal standard .The analytes were separated on a C18 column with a mobile phase consisting of water-acetonitrile containing 0.1%（v/v） formic acid at a flow rate of 0.3 ml/min.The mass spectrometer was operated in a selected reaction monitoring （ SRM ） mode with a positive electrospray ionization （ESI） interface.The plasma concentration-time curve was drawn and pharmacokinetic parameters were calculated by DAS 2.0.Results The linear range was from 2 to 1000 ng/ml with a sensitivity of 2 ng/ml as the lower limit of quantification . The intra-day and inter-day precisions , recoveries and matrix effects at three spiked levels were all suited to the determina-tion of biological samples.After oral administration of S-071031B, the Cmax of S-071031B was （287.2 ±50.8） μg/L and the Tmax was （0.8 ±0.3） h, with a t1/2of （2.9 ±0.6） h and an AUC（0-∞）of （1372.6 ±255.3） μg/L· h.Conclusion This method is sensitive and specific enough for determination of S-071031 B in rat plasma to facilitate the study of its phar-macokinetics .