用UPLC-MS/MS法测定人血浆中盐酸贝尼地平的浓度  

Determination of the concentration of benidipine hydrochloride in human plasma by UPLC-MS/MS

作　　者：赵梦然 杨乐[3] 张彦景 佟彬良[2] 杨谦谦[2] 赵云丽 ZHAO Meng-ran;YANG Le;ZHANG Yan-jing;TONG Bin-liang;YANG Qian-qian;ZHAO Yun-li(College of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110000,Liaoning Province,China;Department of Clinical Medicine,The First Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei Province,China;Department of Pharmacology,Hebei Medical University,Shijiazhuang 050017,Hebei Province,China)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110000 [2]河北医科大学第一医院临床药学部,河北石家庄050000 [3]河北医科大学药理学教研室,河北石家庄050017

出　　处：《中国临床药理学杂志》2023年第24期3648-3652,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的 建立测定人血浆中盐酸贝尼地平浓度的超高效液相色谱-质谱(UPLC-MS/MS)方法,并用于健康受试者的药代动力学研究。方法 人血浆样品经乙酸乙酯萃取预处理。色谱柱:Shim-pack XR-ODSⅢ(1.6μm,2.0 mm×50.0 mm),流动相:水(5 mmol·L^(-1)醋酸铵)-乙腈,等度洗脱,流速:0.3 mL·min^(-1)。三重四极杆质谱电喷雾离子源,多反应监测模式(MRM)正离子MRM扫描,盐酸贝尼地平-d5同位素作为内标。考察该方法的专属性、标准曲线、定量下线、精密度、回收率、稳定性和基质效应。结果 盐酸贝尼地平在0.01~15.00 ng·mL^(-1)线性关系良好(r>0.999),提取回收率78.21%~83.14%,精密度相对标准偏差≤6.42%,稳定性良好,无明显基质效应。6例健康受试者前后2次分别各口服盐酸贝尼地平1片(8 mg),平均T_(1/2)、T_(max)和C_(max)分别为(4.57±2.92) h,(1.08±0.52) h和(7.28±1.87) ng·mL^(-1)。结论 该方法灵敏度高、分析时间短、准确度好、操作简单,可用于盐酸贝尼地平药代动力学及生物等效性研究。Objective To develop an ultra performance liquid chromatography/tandem mass spectrometry(UPLC-MS/MS) method for the determination of benidipine in human plasma and apply it to the pharmacokinetics study of healthy volunteers.Methods Human plasma samples were pretreated with ethyl acetate extraction.The chromatographic column was Shim-pack XR-ODS Ⅲ(1.6 μm,2.0mm ×50.0 mm),The mobile phase consisted of water(5 mmol·L^(-1)ammonium acetate)-acetonitrile with a isocratic elution at a flow rate of0.3 mL·min^(-1).Detection was performed using an electrospray ionization source operating in positive ion multiple reaction monitoring mode,and d5 isotope of benidipine hydrochloride was used as the internal standard.To validate the method,specificity,linearity,quantification limit,precision,recovery,stability and matrix effect were determined.Results Benedipine had a good linear relationship(r>0.999) in the concentration range of 0.01-15.00 ng · mL^(-1),the extraction recovery was 78.21%-83.14%,the precision relative standard deviation was less than 6.42%,and the stability was good.No significant matrix effects were found during the determination.Six healthy volunteers took one tablet of benidipine hydrochloride(8 mg) orally for two times,the mean T_(1/2),T_(max) and C_(max) of benidipine hydrochloride orally administered to subjects were(4.57±2.92) h,(1.08±0.52) h and(7.28±1.87)ng·mL^(-1),respectively.Conclusion The method has high sensitivity,high efficiency,good accuracy and simple operation,which can be used for the pharmacokinetics and bioequivalence study of benidipine.

关 键 词：盐酸贝尼地平 超高效液相色谱-质谱法 血药浓度 药代动力学 

分 类 号：R97[医药卫生—药品]