LC—MS／MS法测定微孔型盐酸文拉法辛渗透泵控释片在比格犬体内生物利用度及生物等效性的研究  

The study of the bioavailability and bioequivalence of venlafaxine hydrochcloride osmotic porosity pump release tablets in beagles detected by LC - MS/MS method

作　　者：刘毅[1] 渠静[2] 王锦刚 

机构地区：[1]中国人民解放军总医院海南分院麻醉科,海南三亚572013 [2]徐州医学院药学院,江苏徐州221004 [3]北京可信必成医药科技发展有限公司,北京100190

出　　处：《徐州医学院学报》2014年第10期641-646,共6页Acta Academiae Medicinae Xuzhou

摘　　要：目的利用LC—MS／MS法对自制微孔型盐酸文拉法辛渗透泵控释片在比格犬体内的生物利用度及生物等效性进行研究。方法8只比格犬随机分成2组，分别单剂量口服受试制剂（自制微孔型盐酸文拉法辛渗透泵控释片）和参比制剂（市售盐酸文拉法辛缓释胶囊），在相应的时间点采集血样，经1周的清洗期后交叉给药。采用LC—MS／MS法测定比格犬体内文拉法辛血药浓度，使用WinNonlin5．2应用软件计算药代动力学参数。结果受试制剂和参比制剂各药代动力学参数：半衰期（T1/2）分别为2．86、3．15h，达峰时间（Tmax）分别为13．25、7．50h，达峰浓度（Cmax）分别为253．72、127．14ng／ml，曲线下面积（AUC（0-t））分别为3126．14、1552．80ng·ml^-1·h^-1，平均滞留时间（MRT（0-∞））分别为13．79、10．35h。结论该测试方法简便可行，受试制剂与参比制剂在吸收的速度和程度方面有显著性差异，受试制剂生物利用度较高，二者生物不等效。Objective To develop a quick and effective liquid chromatography tandem mass spectrometry （ HPLC - MS/MS） method for the determination of venlafaxine in beagle＇s plasma and to study its bioavailability and bioequivalence. Methods Eight beagle dogs were randomly divided into two groups. One group was given referenee preparation and another was given tested preparation. Plasma samples were selected at reservation time. Test crossover was taken after one week. Plasma concentration was decteted by LC - MS/MS, then pharmacokinetic parameters were calculated using WinNonlin 5.2. Results The main pharmacokinetic parameters of reference and test preperations were as follows respeetively ： T1/2 2.86 h, 3.15 h; Tmax 13.25 h, 7.50 h; Cmax 253. 72 ng/ml, 127. 14 ng/ml; AUC（0-t）3 126.14 ng· ml^-1· h^- 1, 1 552.80 ng·ml^-1· h^-1 ; MRT（0-∞） 3.79 h, 10.35 h. Conclusion This method is simple and sensitive. The absorption rate of test tablet is higher than that of reference tablet. They are not bioequivalence.

关 键 词：盐酸文拉法辛 微孔型渗透泵控释片 高效液相色谱串联质谱 生物利用度 生物等效性 

分 类 号：R917[医药卫生—药物分析学]