HPLC-MS/MS法同时测定患者全血中他克莫司和五酯胶囊4种主要成分的浓度  

Simultaneous Determination of Tacrolimus and Four Main Compounds of Wuzhi Capsule in Patients’Whole Blood by HPLC-MS/MS

作　　者：岳娇 熊雯 文元新 南峰 袁宇琳 张静 郑萍 张梅[2] 徐源 YUE Jiao;XIONG Wen;WEN Yuanxin;NAN Feng;YUAN Yulin;ZHANG Jing;ZHENG Ping;ZHANG Mei;XU Yuan(Key Laboratory of Chemical Drug Quality Research and Control of Sichuan Drug Administration,Joint Laboratory of Clinical Pharmacology and Biological Sample Testing and Research,Chengdu Institute of Drug Control,Chengdu 610041;State Key Laboratory of Traditional Chinese Medicine Resources with Southwest Characteristics,School of pharmacy,Chengdu University of TCM,Chengdu 611137;Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610032;School of pharmacy,Chengdu Medical College,Chengdu 610083)

机构地区：[1]四川省药品监督管理局化学药品质量研究与控制重点实验室,临床药理学与生物样本检测研究联合实验室,成都市药品检验研究院,四川成都610041 [2]西南特色中药资源国家重点实验室,成都中医药大学药学院,四川成都611137 [3]成都中医药大学附属医院,四川成都610032 [4]成都医学院药学院,四川成都610083

出　　处：《分析科学学报》2024年第2期213-218,共6页Journal of Analytical Science

摘　　要：建立HPLC-MS/MS法同时测定人全血中他克莫司和五酯胶囊4种主要成分五味子甲素、五味子乙素、五味子醇甲、五味子酯甲的浓度,并用于免疫抑制剂他克莫司联用保肝中药五酯胶囊临床药物浓度监测的研究中。采用了WatersAcquity UPLC■BEH C18色谱柱(50×2.1mm,1.7μm),以5mmol/L乙酸铵-0.1%甲酸水溶液为水相,乙腈为有机相,流速为0.3mL/min,柱温60℃。各成分均采用他克莫司同位素化合物(13C,2H4)作为内标(IS),全血样本首先经硫酸锌处理,再加入含内标的乙腈沉淀蛋白,最后离心后取上清液进样,质谱采用电喷雾离子源,以多反应离子监测(MRM)、正离子扫描模式检测。建立的HPLC-MS/MS法在1~100ng/m L范围内,他克莫司和五酯胶囊的4种主要成分色谱响应与浓度相关性良好,定量下限均为1ng/m L;他克莫司、五味子甲素、五味子乙素、五味子醇甲、五味子酯甲以及内标的保留时间分别为2.54、2.33、2.65、1.14、1.56、2.54min;准确度、回收率和经内标校准后的基质效应及稳定性数据均符合相关要求。方法灵敏、专属性强、准确性好,适用于人全血中他克莫司、五味子甲素、五味子乙素、五味子醇甲、五味子酯甲的浓度测定。A HPLC-MS/MS method to simultaneously determine the concentration of tacrolimus and four main components of wuzhi capsule(schisandrin,schisandrin B,schisandrin alcohol A and schisandrin ester A)in human whole blood was established,and used for the clinical drug concentration monitoring of immunosuppressant tacrolimus combined with hepatoprotective Chinese medicine Wuzhi capsule.A Waters Acquity UPLC■BEH C 18 column(50×2.1 mm,1.7μm)was used,with 5 mmol/L ammonium acetate-0.1% formic acid as the aqueous phase and acetonitrile as the organic phase.The flow rate was 0.3 mL/min,and the column temperature was 60℃.Tacrolimus isotope compound(13 C,2H 4)was used as internal standard(IS)for each component.Whole blood samples were treated with zinc sulfate at first,and then acetonitrile containing internal standard was added to precipitate protein.Finally,after centrifugation,the supernatant was taken for injection.Multiple reactive ion monitoring(MRM)mode,and positive ion scanning mode were used with electrospray ion source.The chromatographic responses of tacrolimus and the four main components of Wuzhi capsules were well correlated with the concentration in the range of 1-100 ng/mL,and the lower limits of quantification were all 1 ng/mL.The retention times of tacrolimus,schisandrin,schisandrin B,schisandrin alcohol A,schisandrin esteryl A and internal standard were 2.54,2.33,2.65,1.14,1.56,2.54 min,respectively.The accuracy,recovery and matrix effect after internal standard calibration were qualified.The stability data meet the relevant requirements.The method is sensitive,specific and accurate to be suitable for determination of concentration of tacrolimus,schisandrin,schisandrin B,schisandrin alcohol A and chisandrin esteryl A in human whole blood.

关 键 词：HPLC-MS/MS 他克莫司 五酯胶囊 治疗药物监测 

分 类 号：O657.63[理学—分析化学]