HPLC-MS/MS测定人血浆中伏立康唑质量浓度及其生物等效性研究  

Determination of Voriconazole in Human Plasma and Its Bioequivalence by HPLC-MS/MS

作　　者：向瑾[1] 余勤[1] 梁茂植[1] 秦永平[1] 南峰[1] 

机构地区：[1]四川大学华西医院临床药理研究室,成都610041

出　　处：《四川大学学报（医学版）》2018年第1期102-106,共5页Journal of Sichuan University(Medical Sciences)

摘　　要：目的建立高效液相色谱-串联质谱(HPLC-MS/MS)法测定人血浆中伏立康唑的方法,并进行伏立康唑片生物等效性研究。方法采用双周期随机交叉自身对照试验设计,48例健康男性受试者分别单次空腹口服两种伏立康唑片200mg,采用HPLC-MS/MS法测定人血浆中伏立康唑质量浓度,以WinNonlin○R6.1软件计算主要药动学参数,并评价两种伏立康唑片的生物等效性。结果伏立康唑标准曲线范围均为1~5 000ng/mL,日内及日间精密度[相对标准偏差(RSD)]均小于11%,准确度在100.00%~109.73%之间,以内标基质效应校准后的伏立康唑基质效应RSD小于15%,萃取回收率大于50%,各项稳定性考察结果合格。伏立康唑峰浓度(Cmax)和药-时曲线下面积(AUC0-t、AUC0-∞)的90%置信区间在80.00%~125.00%等效区间之内,受试制剂与参比制剂间达峰时间(Tmax)差异无统计学意义(P>0.05)。结论所建立的HPLC-MS/MS方法可用于人血浆中伏立康唑质量浓度的测定,伏立康唑片受试制剂与参比制剂生物等效。Objective To develop a high performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） method for the determination of voriconazole in human plasma and its bioequivalence. Methods 48 healthy male volunteers received a single dose of 200 mg vorieonazole tablets in a two period （with two preparations） and randomized crossover bioequivalence study. Their plasma voriconazole was determined using HPLC-MS/MS. The pharmacokinetic parameters and bioequivalence of the two preparations were calculated with WinNonlin 6.1. Results The calibration curve of voriconazole ranged from 1 to 5 000 ng/mL. The HPLC-MS/MS method had less than 11% intra- and inter-day relative standard deviation （RSD）, with 100. 00% to 109. 73% accuracies. The RSD of the matrix effect of voriconazole adjusted with internal standard was less than 15%. The extract recoveries exceeded 50% with good stability. The 90~/6o confidence intervals for the peak concentration （Cmax） and the area under the curve （AUC0-t and AUC0-∞） of voriconazole fell into the bioequivalence range of 80.00%-125.00%. There was no significant difference in peak time （Tmax） between the two preparations. Conclusion HPLC MS/MS can be used for determination of voriconazole in human plasma. The two tested preparations of voriconazole are bioequivalent.

关 键 词：伏立康唑 高效液相色谱-串联质谱法 血药浓度 生物等效性研究 

分 类 号：O657.63[理学—分析化学] R969[理学—化学]