芬太尼口颊片在比格犬体内的药动学研究
x

请在关注微信后,向客服人员索取文件

篇名: 芬太尼口颊片在比格犬体内的药动学研究
TITLE:
摘要: 目的:建立比格犬体内枸橼酸芬太尼血药浓度的测定方法,并进行芬太尼口颊片的药动学研究。方法:取6只比格犬给予芬太尼口颊片1片(675 μg/片,含服),分别于给药后2、5、10、15、30、45、60、90、120、240、360、480、720 min取静脉血1 mL,经甲醇沉淀后,采用液相色谱-串联质谱(LC-MS/MS)法[色谱条件:色谱柱为Agilent C18,流动相为甲醇-0.02%甲酸水溶液(95 ∶ 5,V/V),流速为0.5 mL/min,进样量为5 μL,柱温为30 ℃;质谱条件:采用电喷雾电离源,正离子多反应监测,检测离子为枸橼酸芬太尼质荷比(m/z)337.1→188.0、卡马西平(内标)m/z 237.1→194.1],测定枸橼酸芬太尼的血药浓度,并采用DAS 2.0软件计算药动学参数。结果:枸橼酸芬太尼检测质量浓度的线性范围为1.0~325.0 ng/mL(r=0.998),精密度试验的日内RSD<5%(n=6),日间RSD<6%(n=3);平均回收率为(94.65±6.32)%~(99.21±3.24)%(n=6);基质效应的RSD<15%(n=6),稳定性试验的RE在±6.2%内(n=3)。芬太尼口颊片在比格犬体内的药动学参数tmax为(32.5±6.1) min,t1/2为(211.8±47.4) min,cmax为(40.3±1.9) ng/mL,CLz/F为(0.006±0.001) L/(min·kg),AUC0-720 min为(7 564.0±1 576.7) ng·min/mL(n=6)。结论:本方法简便、可行、准确。芬太尼口颊片在比格犬体内具有良好的速释、缓释双相释药特性。
ABSTRACT: OBJECTIVE: To establish a method for blood concentration determination of Fentanyl buccal tablet in Beagle dogs, and to study its pharmacokinetics. METHODS: A total of 6 Beagle dogs were given Fentanyl buccal tablet 1 tablet (675 μg/tablet, buccally). The blood samples were collected 2, 5, 10, 15, 30, 45, 60, 90, 120, 240, 360, 480, 720 min after administration. After precipitated by methanol, LC-MS/MS method [the determination was performed on Agilent C18 column with mobile phase consisted of methanol-0.02% formic acid aqueous solution (95 ∶ 5, V/V) at the flow rate of 0.5 mL/min. The sample size was 5 μL and the column temperature was 30 ℃. Mass spectrometric conditions: electrospray ionization source in the multiple reaction monitoring mode was used to detect ions, fentanyl citrate: m/z 337.1→188.0; carbamazepine (internal standand): m/z 237.1→194.1] was used to determine the blood concentration of fentanyl citrate; the pharmacokinetic parameters were calculated by using DAS 2.0 software. RESULTS: The linear range of fentanyl citrate were 1.0-325.0 ng/mL(r=0.998); inter-day RSDs of precision test were lower than 5% (n=6), and intra-day RSDs were lower than 6% (n=3); average recoveries were (94.65±6.32)%-(99.21±3.24)% (n=6). RSDs of matrix effect was lower than 15% (n=6); RE of stability tests were within ±6.2% (n=3). The pharmacokinetic parameters of Fentanyl buccal tablet in Beagle dogs included that tmax was (32.5±6.1) min; t1/2 was (211.8±47.4) min; cmax was (40.3±1.9) ng/mL; CLz/F was (0.006±0.001) L/(min·kg); AUC0-720 min was (7 564.0±1 576.7) ng·min/mL(n=6). CONCLUSIONS: The method is simple, feasible and accurate. Fentanyl buccal tablet have good fast-release and slow-release biphasic release characteristics in Beagle dogs.
期刊: 2019年第30卷第15期
作者: 何京亚,桑广泽,乔友备,贺欣,余喆,吴红
AUTHORS: HE Jingya,SANG Guangze,QIAO Youbei,HE Xin,YU Zhe,WU Hong
关键字: 芬太尼;口颊片;液相色谱-串联质谱法;比格犬;血药浓度;药动学
KEYWORDS: Fentanyl; Buccal tablet; LC-MS/MS; Beagle dogs; Blood concentration; Pharmacokinetics
阅读数: 181 次
本月下载数: 0 次

* 注:未经本站明确许可,任何网站不得非法盗链资源下载连接及抄袭本站原创内容资源!在此感谢您的支持与合作!