摘要
目的：建立液相色谱-串联质谱法（HPLC-MS/MS法）测定人血浆及尿液中贝他斯汀的药物浓度,并用于苯磺酸贝他斯汀片临床药动学研究。方法：血浆/尿液经固相萃取后,采用HPLC-MS/MS测定。色谱柱为AtlantisTMHILIC Silica色谱柱（2.1 mm×150 mm,3μm）,以乙腈-水-200 mmol·L^-1甲酸铵溶液（p H 3.0）（75∶20∶5）为流动相,流速0.3 m L·min-1,柱温30℃;质谱采用ESI＋,多重反应监测（MRM）模式;选择检测离子反应对为m/z 388.8→201.7（贝他斯汀）,m/z 299.9→226.7（甲氧氯普胺,内标）。结果：人血浆中贝他斯汀的线性范围为1-400 ng·m L^-1,定量下限为1 ng·m L^-1。批内、批间精密度分别小于7.9%和10.4%,专属性良好。在临床药动学研究中,应用此法检测了12名健康受试者口服5 mg苯磺酸贝他斯汀片后血浆及尿液中贝他斯汀的浓度。结论：本方法简便、准确,专属性强,可满足苯磺酸贝他斯汀片的临床药动学研究。
Objective： To establish a sensitive and specific liquid chromatograph -tandem mass spectrometric （HPLC -MS/MS）method for the determination of bepotastine in human plasma and urine. Methods：The sample was prepared by solid phase extraction. The AtlantisTM HILIC Silica column（2. 1 mm× 150 mm,3 μm）was used with the mobile phase of acetonitrile- water-200 mmol ·L-1 ammonium formate（pH 3.0）（75： 20：5 ）at the flow rate of 0. 3 mL ·min^- 1 The column temperature was 30 ℃. The detection was performed by electrospray ioniza- tion mass spectrometry in the multiple reaction monitoring（MRM） mode. The positive ion scan mode was used to de- tect bepotastine and metoclopramide （internal standard, IS）. The MRM transitions of m/z 388.8→201.7 and 299.9 →226.7 were used to quantify bepotastine and IS, respectively. Results： The assay was linear in the concentration range of 1 -400 ng· mL^-1 for bepotastine in human plasma. The limit of quantification was 1 ng· mL^-1. The intra - day and inter - day RSDs in plasma were lower than 7.9% and 10.4% ,respectively. The method was successfully applied to a pharmacokinetic study of detection of bepotastine in human plasma and urine of healthy volunteers after oral administration of bepotastine besilate tablets （5 mg）. Conclusion： The HPLC - MS/MS method is simple, accurate and selective for the clinical pharmacokinetie study of bepotastine besilate tablets.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2014年第12期2139-2144,共6页
Chinese Journal of Pharmaceutical Analysis
