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肝移植术后受者依维莫司血药浓度检测体系的建立 被引量:1

Establishment of a blood concentration detection system for everolimus in recipients after liver transplantation
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摘要 目的建立测定肝移植受者全血中依维莫司浓度的超高效液相色谱-串联质谱法(UPLC-MS/MS)检测体系。方法用甲醇和硫酸锌沉淀样本蛋白质,以依维莫司-D4为内标物。采用Phenomenex Kinetex PFP色谱柱;流动相A:水(含有2 mmol/L甲酸铵和0.1%甲酸),流动相B:甲醇(含有2 mmol/L甲酸铵和0.1%甲酸),梯度洗脱,流速1 mL/min,柱温50℃,进样量1μL。在正离子模式下,以多反应监测方式进行定量测定。该UPLC-MS/MS检测体系只需100μL全血,无需复杂的样品制备即可达到足够的定量下限,总运行时间4.5 min内。采用依维莫司峰面积/依维莫司-D4峰面积(y)和依维莫司浓度/依维莫司-D4浓度(x)进行线性回归(1/x^(2))分析,计算校准函数,分析其准确度和线性关系。并应用UPLC-MS/MS检测5例肝移植术后受者血样本的依维莫司血药谷浓度。结果依维莫司在血药浓度1~100 ng/mL范围内的质控准确度都在15%以内,线性关系良好(R2>0.990)。测定的5例肝移植受者血样本的依维莫司血药谷浓度为3.77~9.27 ng/mL。结论本研究建立的UPLC-MS/MS检测体系测定肝移植受者全血中依维莫司血药浓度准确度高、样品处理方法简便、检测时间短,适用于肝移植术后受者血样本中依维莫司的药物浓度监测。 Objective To establish a detection system of ultra high performance liquid chromatographytandem mass spectrometry(UPLC-MS/MS)for everolimus concentration in whole blood of liver transplant recipients.Methods The proteins of samples were precipitated with methanol and zinc sulfate,and everolimus-D4 was used as the internal standard.Phenomenex Kinetex PFP column was used.The mobile phase A was water(containing 2 mmol/L ammonium formate and 0.1%formic acid),and the mobile phase B was methanol(containing 2 mmol/L ammonium formate and 0.1%formic acid).The gradient elution was performed with the flow rate of 1 mL/min,the column temperature of 50℃ and the injection volume of 1μL.The multi-reaction monitoring mode was used to quantitatively analyze with electrospray positive ionization.The UPLC-MS/MS detection system required only 100μL of whole blood,and could achieve a sufficient lower limit of quantification without complicated sample preparation.The total running time was within 4.5 min.Linear regression(1/x^(2))analysis was performed using peak area of everolimus/peak area of everolimus-D4(y)and concentration of everolimus/concentration of everolimus-D4(x)to calculate the calibration function and analyze its accuracy and linear relationship.UPLC-MS/MS was used to detect the trough blood concentration of everolimus in blood samples of 5 recipients after liver transplantation.Results The accuracy of quality control was within 15%,and the linear relationship of everolimus was good in the blood concentration range of 1-100 ng/mL(R2>0.990).Trough blood concentration of everolimus measured in blood samples of 5 liver transplant recipients ranged from 3.77 to 9.27 ng/mL.Conclusions The detection system of UPLC-MS/MS in this study is suitable for monitoring the concentration of everolimus in whole blood of liver transplant recipients because of its high accuracy,simple sample processing method and short detection time.
作者 陶斯湄 黄际薇 李海波 张英才 杨扬 Tao Simei;Huang Jiwei;Li Haibo;Zhang Yingcai;Yang Yang(Department of Pharmacy,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China;不详)
出处 《器官移植》 CAS CSCD 北大核心 2021年第5期595-600,共6页 Organ Transplantation
基金 广东省重点领域研发计划项目(2019B020236003)。
关键词 依维莫司 超高效液相色谱-串联质谱法(UPLC-MS/MS) 高效液相色谱法(HPLC) 肝移植 血药浓度 钙调磷酸酶抑制剂(CNI) 哺乳动物雷帕霉素靶蛋白(mTOR) 西罗莫司 Everolimus Ultra high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) High performance liquid chromatography(HPLC) Liver transplantation Blood concentration Calcineurin inhibitor(CNI) Mammalian target of rapamycin(mTOR) Sirolimus
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