液相色谱—串联质谱法测定富马酸依美斯汀在健康人体的血药浓度及其药代动力学

Determination the concentration and pharmacokinetics of emedastine difumarate in healthy volunteers by HPLC-MS-MS

目的建立液相色谱-串联质谱法测定富马酸依美斯汀在健康人血浆中的浓度及其药代动力学。方法12名健康志愿受试者单剂量口服富马酸依美斯汀缓释胶囊2mg，血浆样品经乙酸乙酯萃取分离后，用HPLC—MS—MS法测定富马酸依美斯汀血浆浓度。结果最低检测限为0．02ng·mL^-1，在0．05～16．0ng·mL^-1内，质谱响应线性关系良好；萃取绝对回收率均〉80％，日内、日间相对偏差均〈20％。用该法测得药代动力学参数：Cmax为（5．98±1．77）ng·mL^-1，tmax为（4．5±0．5）h，t1／2为（8．27±2．04）h；MRT为（14．3±21．2）h；AUC0-36为（72．43±34．62）h·ng·mL^-1；AUC1→∞为（78．0±39．1）ng·h·mL^-1。结论建立的HPLC—MS—MS法专属、灵敏和准确，可用于富马酸依美斯汀药代动力学研究。

Objective To establish an accurate and sensitive HPLC - MS - MS method for the determination and pharmacokinetic study of emedastine difumarate in plasma. Methods Emedastine difumarate in plasma of 12 healthy Chinese male volunteers after a single oral dose of 2 mg of sustained release capsules was separated by using liquid -liquid extraction with ethyl acetate. The electrospray ionization positive selected reaction monitoring detections for emedastine （difumarate） and prazosine （the internal standard） were used. Results The limit of detection for emedastine difumarate in plasma was 0.02 ng·mL^-1 and a good linearity was obtained in the range of 0.05 ～ 16.0 ng·mL^-1 with the established HPLC- MS- MS method. The extraction recoveries were all over 80%. The relative standard deviations of within -day and between -day determination were less than 20%. The main pharmacokinetic parameters after a single oral dose of 2 mg of emedastine difumarate sustained release capsules were as follows ： Cmax was （5.98 ± 1.77 ） ng·mL^-1, tmax was （4.5±0.5） h, t1/2 was （8.27±2.04） h, MRT was （14.3±21.2） h, AUC0-36 was （72. 43±34. 62） h ·ng·mL^-1, AUC0→∞ was （78.0 ± 39.1 ） ng · h · mL^-1. Conclusion The established HPLC -MS- MS method was shown to be selective, sensitive, and accurate and the pharmacokinetic parameters determined were reliable and important for clinical application.