CAJ | 학술논문

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。
목적：응용액상색보-천련질보법（LC-MS/MS）건립대서혈장중아모서정（S-071031B）농도측정방법，병고찰대서관위급여아모서정후적약대동역학。방법채용LC-MS/MS방법，이염산분배임지좌선체（ L-8021）위내표，C18주위분석주，류동상위함0．1％갑산적수-을정체계，류속위0．3 ml/min，채용전분무정리자（ESI ＋）、선택반응감측（SRM）모식진행검측。회제혈약농도-시간곡선병이용DAS 2．0계산약대동역학삼수。결과대서혈장중내원성잡질불간우아모서정화내표적측정，아모서정적선성범위위2～1000 ng/ml （r2＝0．9965），정량한위2 ng/ml，일내、일간정밀도화준학도，절대회수솔화기질효응균부합생물양품측정수요。대서구복관위후재（0．8±0．3）h체도（287．2±50．8）μg/L적봉치농도，t1/2위（2．9±0．6）h，AUC（0-∞）위（1372．6±255．3）μg/L· h。결론본방법령민도고、특이성호，가용우혈장중아모서정적농도측정급기약대동역학연구。
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 .