To investigate deeply into the preclinical pharmacokinetics and prescription design of esomeprazole, a sensitive, high throughput and robust UHPLC–MS/MS method had been developed and fully validated for the analysis of esomeprazole in dog plasma. Esomeprazole and diazepam (IS) were fast extracted from plasma by alkalified organic solvent, and separated on MP-C₁₈ column with methanol and 0.1% formic acid. The quantification of esomeprazole and IS had been achieved using fragmentation transitions of m/z 346.1 → 198.1 and m/z 285.0 → 193.2 in MRM detection under positive ESI mode. The concentration of esomeprazole in dog plasma was linear with the range of 3.75–500 ng/mL. The precisions of intra- and inter-day were no more than 11.6%, while the accuracies were all within ±9.7% of the nominal values. The recovery was no more than 77.06%, and the matrix effect, stability, dilution integrity tests were all satisfied the currently criterion. Then the method was successfully performed to evaluating pharmacokinetics of esomeprazole and optimizing the prescription of modified esomeprazole with varied addition of sodium bicarbonate. Consequently, a pharmacokinetic study of three doses esomeprazole with the optimized addition of sodium bicarbonate in dogs has been successfully researched for the first time. It could be a promising approach to improve the stabilization of acid-labile esomeprazole and would provide a useful reference for the formulation design of esomeprazole.

为了深入研究埃索美拉唑的临床前药代动力学和处方设计，开发了一种灵敏，高通量且功能强大的UHPLC-MS / MS方法，并已完全验证了狗血浆中埃索美拉唑的分析。用碱化的有机溶剂从血浆中快速提取埃索美拉唑和地西epa（IS），并在MP-C ₁₈色谱柱上用甲醇和0.1％甲酸进行分离。使用m / z 346.1→198.1和m / z的片段化跃迁可实现埃索美拉唑和IS的定量在正ESI模式下的MRM检测中为285.0→193.2。狗血浆中的埃索美拉唑浓度呈线性关系，范围为3.75–500 ng / mL。日内和日间的精度不超过11​​.6％，而精度均在标称值的±9.7％之内。回收率不超过77.06％，基质效果，稳定性，稀释完整性测试均符合现行标准。然后成功地进行了该方法的评价，以评估埃索美拉唑的药代动力学，并通过添加不同的碳酸氢钠来优化修饰的埃索美拉唑的处方。因此，首次成功研究了三种剂量的埃索美拉唑与优化的碳酸氢钠添加在犬中的药代动力学研究。