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右兰索拉唑缓释胶囊在Beagle犬体内的生物等效性研究
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| 篇名： | 右兰索拉唑缓释胶囊在Beagle犬体内的生物等效性研究 |
| TITLE： | |
| 摘要： | 目的：建立测定Beagle犬血浆中右兰索拉唑浓度的方法，评价两种右兰索拉唑缓释胶囊的生物等效性。方法：6只Beagle犬随机分为参比制剂组和受试制剂组，每组3只，采用双周期交叉随机试验（清洗期为1周）设计，分别空腹单次口服右兰索拉唑缓释胶囊参比制剂和受试制剂各60 mg，并于给药前及给药后0.5、1、1.5、2、2.5、3、3.5、4、4.5、5、6、7、8、10、12 h自前肢头静脉取血2 mL，采用液相色谱-串联质谱法（LC-MS/MS）测定Beagle犬血浆中右兰索拉唑的浓度。以奥美拉唑为内标，色谱柱为Inertsil ODS，流动相为甲醇-0.1％甲酸溶液（90 ∶ 10，V/V）；采用电喷雾离子源，以多反应监测模式进行正离子扫描，用于定量分析的离子对分别为m/z 369.9→251.7（右兰索拉唑）、m/z 345.7→197.9（内标）。采用DAS 3.1.6软件计算药动学参数，以双侧t检验及（1－2α）％置信区间（CI）法、Wilcoxon检验考察两种制剂的生物等效性。结果：右兰索拉唑血药浓度的线性范围为10～4 000 ng/mL，定量下限为10 ng/mL；批内、批间RSD＜10％，准确度为94.40％～105.20％。空腹单次口服参比制剂或受试制剂的AUC0-t分别为（8 892.48±1 399.67）、（8 683.71±1 167.88）ng·h/mL，AUC0-∞分别为（8 925.73±1 399.64）、（9 053.08±1 553.46）ng·h/mL，tmax分别为（3.50±0.71）、（3.75±1.21）h，cmax分别为（2 980.00±487.40）、（2 863.33±331.34）ng/mL。受试制剂AUC0-t、AUC0-∞、cmax的90％CI均在参比制剂相应参数的80％～125％范围内，两制剂tmax间的差异无统计学意义（P＞0.05）。结论：本研究建立的LC-MS/MS法适用于Beagle犬血浆中右兰索拉唑浓度的测定，且两种制剂在Beagle犬体内具有生物等效性。 |
| ABSTRACT： | OBJECTIVE： To establish a method for the determination of dexlansoprazole concentration in plasma of Beagle dogs， and to evaluate bioequivalence of 2 kinds of Dexlansoprazole sustained-release capsules. METHODS： A total of 6 Beagle dogs were randomly divided into reference preparation group and test preparation group， with 3 dogs in each group. In double cycle cross randomized trial （cleaning period lasting for one week） design， they were given reference preparation and test preparation of Dexlansoprazole sustained-release capsules 60 mg once. The blood sample 2 mL of forelimb vein were collected before medication， 0.5， 1， 1.5， 2， 2.5， 3， 3.5， 4， 4.5， 5， 6， 7， 8， 10， 12 h after medication， respectively. The concentration of dexlansoprazole in plasma of Beagle dogs was determined by LC-MS/MS. Using omeprazole as internal standard， the determination was performed on Inertsil ODS with mobile phase consisted of methanol-0.1％ formic acid solution （90 ∶ 10，V/V）. ESI was used for positive ion scanning by multiple reaction monitoring mode. The ion pair for quantitative analysis were m/z 369.9→251.7 （dexlansoprazole） and m/z 345.7→197.9 （internal standard）， respectively. The pharmacokinetic parameters were calculated by using DAS 3.1.6 software. The bioequivalence of two preparations were investigated by bilateral t test，（1-2α）confidence interval （CI） method and Wilcoxon test. RESULTS： The linear range of dexlansoprazole concentration was 10-4 000 ng/mL. The lower limit of quantitation was 10 ng/mL； RSDs of inter-batch and intra-batch were lower than 10％. The accuracy ranged 94.40％-105.20％. The pharmacokinetic parameters of reference preparation or test preparation of single fasting dose were as follows： AUC0-t were （8 892.48±1 399.67），（8 683.71±1 167.88）ng·h/mL，AUC0-∞ were （8 925.73±1 399.64），（9 053.08±1 553.46）ng·h/mL，tmax were （3.50±0.71），（3.75±1.21）h，cmax were （2 980.00±487.40），（2 863.33±331.34）ng/mL， respectively. 90％CI of AUC0-t， AUC0-∞ and cmax for test preparation were 80％-125％ of corresponding parameters of reference preparation； there was no statistical significance in tmax between 2 preparations（P＞0.05）. CONCLUSIONS： LC-MS/MS is suitable for the determination of dexlansoprazole concentration in Beagle dogs plasma. Moreover， the two preparations are bioequivalent in Beagle dogs． |
| 期刊： | 2018年第29卷第16期 |
| 作者： | 喻明洁，戴青，向荣凤，熊丽蓉，陈勇川 |
| AUTHORS： | YU Mingjie，DAI Qing，XIANG Rongfeng，XIONG Lirong，CHEN Yongchuan |
| 关键字： | 右兰索拉唑；缓释胶囊；液相色谱-串联质谱法；药动学；生物等效性 |
| KEYWORDS： | Dexlansoprazole； Sustained-release capsules； LC-MS/MS； Pharmacokinetics； Bioequivalence |
| 阅读数： | 311 次 |
| 本月下载数： | 10 次 |
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