摘要
目的:建立UPLC-MS/MS法测定SD大鼠血浆中喹硫平的浓度,并用于五酯胶囊对喹硫平在大鼠体内药动学的研究。方法:将30只SD大鼠随机分为5组,单独给药喹硫平组(A,40 mg·kg^(-1)),多次五酯胶囊(150 mg·kg^(-1))合并喹硫平组(B,40 mg·kg^(-1))、单次低、中、高(75,150,300 mg·kg^(-1))剂量五酯胶囊合并喹硫平组(C、D、E组,40 mg·kg^(-1))。于给药前与给药后0.25,0.5,0.75,1,1.5,2,4,6,12,24 h眼底静脉丛采血0.5 mL。采用UPLC-MS/MS法检测大鼠血浆中喹硫平的浓度,并运用DAS2.0药动学软件计算药动学参数,t检验进行统计分析。结果:喹硫平在5~2 000 ng·mL^(-1)范围内呈良好的线性关系(r=0.999 3),日内和日间精密度均小于8.90%,准确度为98.75%~106.82%,回收率为98.11%~103.47%,血浆样品稳性好。联用五酯胶囊时,大鼠体内喹硫平CL、Cmax、AUC0-t、AUC0-∞显著升高(P<0.01),而Tmax(h)、t1/2、MRT0-∞(h)均无显著性差异。结论:UPLC-MS/MS测定方法灵敏度高、专属性强、快速高效。五酯胶囊可影响喹硫平在大鼠体内药代动力学过程,使喹硫平在大鼠体内的血药浓度和生物利用度升高。
OBJECTIVE To establish an UPLC-MS/MS method for determining the concentration of quatiapine and examine the pharmacokinetics of quatiapine in rat plasma after co-dosing with Wuzhi Capsules. METHODS A total of 30 Sprague-Dawley(SD)rats were randomly divided into 5 groups of quetiapine alone(A,40 mg·kg^(-1)),multiple Wuzhi Capsules(150 mg·kg^(-1))plus quetiapine(B,40 mg·kg^(-1))and single low/medium/high-dose Wuzhi Capsules(75/150/300 mg·kg^(-1))plus quetiapine(C/D/E,40 mg·kg^(-1)).Before and after dosing,0.5 mL blood samples of intraocular canthal venous plexus were collected at 0.25,0.5,0.75,1,1.5,2,4,6,12,24 h.The plasma concentration of quetiapine was determined by UPLC-MS/MS,its pharmacokinetic parameters were fitted by DAS2.0 software and statistical analysis was performed by t-test.RESULTS This method exhibited an excellent linearity over a concentration range of 5-2 000 ng·mL^(-1)(r=0.999 3).The intra/inter-day value was within 8.90% with an accuracy of 98.75%-106.82%.The extraction recoveries were 98.11%-103.47%and plasma samples stablized.When co-dosing with Wuzhi Capsules,CL,Cmax,AUC0-t and AUC0-∞ of quetiapine increased markedly(P<0.01)while no significant difference existed in Tmax(h),t1/2 or MRT0-∞(h).CONCLUSION Fast and efficient,the method of UPLC-MS/MS had a high sensitivity and a strong specificity.The pharmacokinetics of quetiapine are influenced by Wuzhi Capsules so as to boost blood concentration and bioavailability of quetiapine in rats.
作者
董文燊
林芝
陈颖
李清
瞿发林
汪慧贤
DONG Wen-shen;LIN Zhi;CHEN Ying;LI Qing;QU Fa-lin;WANG Hui-xian(Department of Pharmacy,No.904 Hospital of People's Liberation Army,Jiangsu Changzhou 213003,China;Hanlin College of Pharmacy,Nanjing University of Traditional Chinese Medicine,Jiangsu Taizhou 225300,China)
出处
《中国医院药学杂志》
CAS
北大核心
2021年第2期144-148,共5页
Chinese Journal of Hospital Pharmacy
基金
无锡市科技发展计划项目(编号:N20202036)。
