Xia Hua-Ling, Zhao Xin-Jie, Zhang Yu-Ji, Su Xiao-Hang, Sun Bo, Qiu Xiang-Jun
Luoyang Orthopedic-Traumatological Hospital of Henan Province, Henan Provincial Orthopedic Hospital, Luoyang 471003, China.
School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang 471023, China.
Evid Based Complement Alternat Med. 2021 Nov 26;2021:4181196. doi: 10.1155/2021/4181196. eCollection 2021.
A sensitive high-performance liquid chromatography (HPLC-UV) method for determination of omeprazole in beagle dog plasma was developed and to investigate the effect of Sijunzi pills (SJZPs) on the pharmacokinetics of omeprazole in beagle dogs. The beagle dog plasma was extracted with ethyl acetate and n-hexane under alkaline conditions. Omeprazole and internal standard (IS, fluconazole) were separated on an XDB-C18 column, and acetonitrile and 0.1% trifluoroacetic acid were used as the mobile phase. Omeprazole and IS were detected by using a diode array detector. This experiment adopts the experimental design of double-cycle self-control. In the first cycle (group A), six beagle dogs were given omeprazole 0.67 mg/kg orally in a single dose. In the second period (group B), the same six beagle dogs were orally given SJZPs 0.2 g/kg twice a day for 7 consecutive days, and then, omeprazole was orally given. At the different time points after omeprazole was given in the two periods, the blood samples were collected. The concentration of omeprazole was detected by the developed HPLC method. DAS 2.0 was used to calculate the pharmacokinetic parameters of omeprazole. Under the current experimental conditions, this UPLC method showed good linearity in the detection of omeprazole. Interday and intraday precision did not exceed 10%, and the range of accuracy values were from -1.43% to 2.76%. The results of extraction recovery and stability met the requirements of FDA approval guidelines of bioanalytical method validation. The of omeprazole in group B was 61.55% higher than that in group A, and the AUC and AUC of omeprazole in group B were 63.96% and 63.65% higher those that in group A, respectively. At the same time, the clearance (CL) and apparent volume of distribution (Vd) decreased in group B. In this study, an HPLC method for the determination of plasma omeprazole concentration was established. SJZPs could inhibit the metabolism of omeprazole and increase the concentration of omeprazole in beagle dogs. It is suggested that when SJZPs are combined with omeprazole, attention should be paid to the herb-drug interactions and possible adverse reactions.
建立了一种灵敏的高效液相色谱法（HPLC-UV）用于测定比格犬血浆中的奥美拉唑，并研究四君子丸（SJZPs）对奥美拉唑在比格犬体内药代动力学的影响。比格犬血浆在碱性条件下用乙酸乙酯和正己烷萃取。奥美拉唑和内标（IS，氟康唑）在XDB-C18柱上分离，乙腈和0.1%三氟乙酸用作流动相。使用二极管阵列检测器检测奥美拉唑和内标。本实验采用双周期自身对照的实验设计。在第一个周期（A组），6只比格犬单次口服0.67mg/kg奥美拉唑。在第二个周期（B组），相同的6只比格犬每天口服0.2g/kg SJZPs，连续7天，然后口服奥美拉唑。在两个周期中给予奥美拉唑后的不同时间点采集血样。采用所建立的HPLC方法检测奥美拉唑浓度。使用DAS 2.0计算奥美拉唑的药代动力学参数。在当前实验条件下，该UPLC方法在检测奥美拉唑时显示出良好的线性。日间和日内精密度均不超过10%，准确度值范围为-1.43%至2.76%。萃取回收率和稳定性结果符合FDA生物分析方法验证批准指南的要求。B组中奥美拉唑的 比A组高61.55%，B组中奥美拉唑的AUC和AUC分别比A组高63.96%和63.65%。同时，B组的清除率（CL）和表观分布容积（Vd）降低。本研究建立了一种测定血浆中奥美拉唑浓度的HPLC方法。SJZPs可抑制奥美拉唑的代谢并增加比格犬体内奥美拉唑的浓度。建议当SJZPs与奥美拉唑合用时，应注意草药-药物相互作用及可能的不良反应。 （原文中部分内容缺失，已根据上下文尽量完整翻译）
