Li Xiuqi, Liu Shupeng, Yu Mengyang, Xi Wanlin, Wu Xiaofei, Liu Dan, Liu Aijing, Wang Hongyun
Clinical Pharmacology Research Center, Peking Union Medical College Hospital, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People's Republic of China.
School of Life Science and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, Liaoning, 110000, People's Republic of China.
Drug Des Devel Ther. 2025 Feb 11;19:955-969. doi: 10.2147/DDDT.S493911. eCollection 2025.
Proton pump inhibitors (PPIs) and potassium competitive acid blockers (P-CABs) are widely used to treat acid-related diseases (ARDs). Precisely quantifying their plasma levels is crucial for clinical pharmacokinetic assessments and therapeutic drug monitoring.
This study aimed to establish a generic and efficient ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay for the determination of five PPIs (esomeprazole, rabeprazole, ilaprazole, lansoprazole, and pantoprazole) and the P-CAB (vonoprazan) in human plasma.
The six analytes were extracted from human plasma via protein precipitation and a single dilution step. Detection was performed on a triple quadrupole tandem mass spectrometer with positive electrospray ionization. Chromatographic separation was achieved on the ACQUITY UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) using gradient elution. The mobile elution was composed of 0.2% formic acid in acetonitrile (mobile phase A), 0.1% ammonium hydroxide and 10 mmol/L ammonium formate in deionized water (mobile phase B). The flow rate was 0.4 mL/min, the run time was 4.5 minutes, and the injection volume was 20 µL.
RESULTS & CONCLUSIONS: The method exhibited excellent linearity across the ranges of 0.2-200 ng/mL for PPIs and 0.5-500 ng/mL for the P-CAB. Both intra- and inter-day precision and accuracy were within the acceptance criteria, with precision ranging from 1.1% to 14.6% and accuracy ranging from 0.0% to 14.7%. Extraction recoveries were consistent, ranging from 88.1% to 96.7%, with no significant matrix effects observed. The stability of the six analytes under diverse storage and processing conditions was also confirmed, with both precision and accuracy falling within the acceptable range of 15%. The UPLC-MS/MS assay provided an efficient and reliable approach for the simultaneous determination of six acid-suppressing medications in a single analytical run. It has been successfully applied to the pharmacokinetic studies of PPIs and P-CABs, offering a valuable tool for clinical research and therapeutic drug monitoring.
质子泵抑制剂（PPIs）和钾离子竞争性酸阻滞剂（P-CABs）被广泛用于治疗酸相关性疾病（ARDs）。准确测定它们的血浆水平对于临床药代动力学评估和治疗药物监测至关重要。
本研究旨在建立一种通用且高效的超高效液相色谱-串联质谱（UPLC-MS/MS）分析法，用于测定人血浆中的五种PPIs（埃索美拉唑、雷贝拉唑、艾普拉唑、兰索拉唑和泮托拉唑）以及P-CAB（沃克）。
通过蛋白沉淀和单次稀释步骤从人血浆中提取六种分析物。在配备正电喷雾电离的三重四极杆串联质谱仪上进行检测。使用ACQUITY UPLC BEH C18柱（2.1×50 mm，1.7 µm）通过梯度洗脱实现色谱分离。流动相洗脱液由乙腈中的0.2%甲酸（流动相A）、去离子水中的0.1%氢氧化铵和10 mmol/L甲酸铵（流动相B）组成。流速为0.4 mL/min，运行时间为4.5分钟，进样体积为20 µL。
该方法在PPIs浓度范围为0.2 - 200 ng/mL以及P-CAB浓度范围为0.5 - 500 ng/mL内表现出出色的线性。日内和日间精密度与准确度均在可接受标准范围内，精密度范围为1.1%至14.6%，准确度范围为0.0%至14.7%。提取回收率一致，范围为88.1%至96.7%，未观察到明显的基质效应。还证实了六种分析物在不同储存和处理条件下的稳定性，精密度和准确度均落在15%的可接受范围内。UPLC-MS/MS分析法为在单次分析运行中同时测定六种抑酸药物提供了一种高效且可靠的方法。它已成功应用于PPIs和P-CABs的药代动力学研究，为临床研究和治疗药物监测提供了有价值的工具。
